Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer.
Journal
Experimental & molecular medicine
ISSN: 2092-6413
Titre abrégé: Exp Mol Med
Pays: United States
ID NLM: 9607880
Informations de publication
Date de publication:
04 Jan 2024
04 Jan 2024
Historique:
received:
30
03
2023
accepted:
28
08
2023
revised:
06
08
2023
medline:
5
1
2024
pubmed:
5
1
2024
entrez:
4
1
2024
Statut:
aheadofprint
Résumé
Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 is strongly upregulated by various inflammatory and immunological diseases, including several cancers, Alzheimer's disease, and atherosclerosis. Several studies have shown that CHI3L1 can be considered as a marker of disease diagnosis, prognosis, disease activity, and severity. In addition, the proinflammatory action of CHI3L1 may be mediated via responses to various proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon-γ. Therefore, CHI3L1 may contribute to a vast array of inflammatory diseases. However, its pathophysiological and pharmacological roles in the development of inflammatory diseases remain unclear. In this article, we review recent findings regarding the roles of CHI3L1 in the development of inflammatory diseases and suggest therapeutic approaches that target CHI3L1.
Identifiants
pubmed: 38177294
doi: 10.1038/s12276-023-01131-9
pii: 10.1038/s12276-023-01131-9
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Organisme : National Research Foundation of Korea (NRF)
ID : 2021RIS-001
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Organisme : National Research Foundation of Korea (NRF)
ID : MRC2017R1A5A2015541
Informations de copyright
© 2023. The Author(s).
Références
Ochoa, D. et al. Open targets platform: supporting systematic drug-target identification and prioritisation. Nucleic Acids Res. 49, D1302–D1310 (2021).
pubmed: 33196847
doi: 10.1093/nar/gkaa1027
Koscielny, G. et al. Open targets: a platform for therapeutic target identification and validation. Nucleic Acids Res. 45, D985–D994 (2017).
pubmed: 27899665
doi: 10.1093/nar/gkw1055
Carvalho-Silva, D. et al. Open targets platform: new developments and updates two years on. Nucleic Acids Res. 47, D1056–D1065 (2019).
pubmed: 30462303
doi: 10.1093/nar/gky1133
Snel, B., Lehmann, G., Bork, P. & Huynen, M. A. STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Res. 28, 3442–3444 (2000).
pubmed: 10982861
pmcid: 110752
doi: 10.1093/nar/28.18.3442
von Mering, C. et al. STRING: a database of predicted functional associations between proteins. Nucleic Acids Res. 31, 258–261 (2003).
doi: 10.1093/nar/gkg034
Szklarczyk, D. et al. The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res. 39, D561–D568 (2011).
pubmed: 21045058
doi: 10.1093/nar/gkq973
Szklarczyk, D. et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 45, D362–D368 (2017).
pubmed: 27924014
doi: 10.1093/nar/gkw937
Szklarczyk, D. et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 51, D638–D646 (2023).
pubmed: 36370105
doi: 10.1093/nar/gkac1000
Szklarczyk, D. et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 49, D605–D612 (2021).
pubmed: 33237311
doi: 10.1093/nar/gkaa1074
Bussink, A. P., Speijer, D., Aerts, J. M. & Boot, R. G. Evolution of mammalian chitinase(-like) members of family 18 glycosyl hydrolases. Genetics 177, 959–970 (2007).
pubmed: 17720922
pmcid: 2034658
doi: 10.1534/genetics.107.075846
Boot, R. G., Renkema, G. H., Strijland, A., van Zonneveld, A. J. & Aerts, J. M. Cloning of a cDNA encoding chitotriosidase, a human chitinase produced by macrophages. J. Biol. Chem. 270, 26252–26256 (1995).
pubmed: 7592832
doi: 10.1074/jbc.270.44.26252
Bonneh-Barkay, D. et al. Astrocyte and macrophage regulation of YKL-40 expression and cellular response in neuroinflammation. Brain Pathol. 22, 530–546 (2012).
pubmed: 22074331
doi: 10.1111/j.1750-3639.2011.00550.x
Hakala, B. E., White, C. & Recklies, A. D. Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J. Biol. Chem. 268, 25803–25810 (1993).
pubmed: 8245017
doi: 10.1016/S0021-9258(19)74461-5
Henrissat, B. A classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem. J. 280, 309–316 (1991).
pubmed: 1747104
pmcid: 1130547
doi: 10.1042/bj2800309
Kognole, A. A. & Payne, C. M. Inhibition of Mammalian Glycoprotein YKL-40: IDENTIFICATION OF THE PHYSIOLOGICAL LIGAND. J. Biol. Chem. 292, 2624–2636 (2017).
pubmed: 28053085
pmcid: 5314161
doi: 10.1074/jbc.M116.764985
Volck, B. et al. YKL-40, a mammalian member of the chitinase family, is a matrix protein of specific granules in human neutrophils. Proc. Assoc. Am. Phys. 110, 351–360 (1998).
pubmed: 9686683
Rehli, M., Krause, S. W. & Andreesen, R. Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics 43, 221–225 (1997).
pubmed: 9244440
doi: 10.1006/geno.1997.4778
Hinsinger, G. et al. Chitinase 3-like proteins as diagnostic and prognostic biomarkers of multiple sclerosis. Mult. Scler. 21, 1251–1261 (2015).
pubmed: 25698171
doi: 10.1177/1352458514561906
Francescone, R. A. et al. Role of YKL-40 in the angiogenesis, radioresistance, and progression of glioblastoma. J. Biol. Chem. 286, 15332–15343 (2011).
pubmed: 21385870
pmcid: 3083166
doi: 10.1074/jbc.M110.212514
Faibish, M., Francescone, R., Bentley, B., Yan, W. & Shao, R. A YKL-40-neutralizing antibody blocks tumor angiogenesis and progression: a potential therapeutic agent in cancers. Mol. Cancer Ther. 10, 742–751 (2011).
pubmed: 21357475
pmcid: 3091949
doi: 10.1158/1535-7163.MCT-10-0868
Eurich, K., Segawa, M., Toei-Shimizu, S. & Mizoguchi, E. Potential role of chitinase 3-like-1 in inflammation-associated carcinogenic changes of epithelial cells. World J. Gastroenterol. 15, 5249–5259 (2009).
pubmed: 19908331
pmcid: 2776850
doi: 10.3748/wjg.15.5249
Rathcke, C. N. & Vestergaard, H. YKL-40, a new inflammatory marker with relation to insulin resistance and with a role in endothelial dysfunction and atherosclerosis. Inflamm. Res. 55, 221–227 (2006).
pubmed: 16955240
doi: 10.1007/s00011-006-0076-y
Quintana, E. et al. Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain. Eur. J. Neurol. 25, 1189–1191 (2018).
pubmed: 29797629
doi: 10.1111/ene.13687
Querol-Vilaseca, M. et al. YKL-40 (Chitinase 3-like I) is expressed in a subset of astrocytes in Alzheimer’s disease and other tauopathies. J. Neuroinflamm. 14, 118 (2017).
doi: 10.1186/s12974-017-0893-7
Kumagai, E. et al. Serum YKL-40 as a marker of liver fibrosis in patients with non-alcoholic fatty liver disease. Sci. Rep. 6, 35282 (2016).
pubmed: 27739482
pmcid: 5064386
doi: 10.1038/srep35282
Di Rosa, M., Szychlinska, M. A., Tibullo, D., Malaguarnera, L. & Musumeci, G. Expression of CHI3L1 and CHIT1 in osteoarthritic rat cartilage model. A morphological study. Eur. J. Histochem. 58, 2423 (2014).
pubmed: 25308850
pmcid: 4194398
Di Rosa, M. & Malaguarnera, L. Chitinase 3 Like-1: an emerging molecule involved in diabetes and diabetic complications. Pathobiology 83, 228–242 (2016).
pubmed: 27189062
doi: 10.1159/000444855
He, C. H. et al. Chitinase 3-like 1 regulates cellular and tissue responses via IL-13 receptor alpha2. Cell Rep. 4, 830–841 (2013).
pubmed: 23972995
pmcid: 3988532
doi: 10.1016/j.celrep.2013.07.032
Subramaniam, R., Mizoguchi, A. & Mizoguchi, E. Mechanistic roles of epithelial and immune cell signaling during the development of colitis-associated cancer. Cancer Res. Front. 2, 1–21 (2016).
pubmed: 27110580
pmcid: 4841680
doi: 10.17980/2016.1
Low, D. et al. Chitinase 3-like 1 induces survival and proliferation of intestinal epithelial cells during chronic inflammation and colitis-associated cancer by regulating S100A9. Oncotarget 6, 36535–36550 (2015).
pubmed: 26431492
pmcid: 4742194
doi: 10.18632/oncotarget.5440
Yu, J. E. et al. Anti-Chi3L1 antibody suppresses lung tumor growth and metastasis through inhibition of M2 polarization. Mol. Oncol. 16, 2214–2234 (2022).
pubmed: 34861103
doi: 10.1002/1878-0261.13152
Ciledag, A. et al. High serum YKL-40 level is associated with poor prognosis in patients with lung cancer. Tuberk Toraks 66, 273–279 (2018).
pubmed: 30683021
doi: 10.5578/tt.67319
Hamilton, G., Rath, B. & Burghuber, O. Chitinase-3-like-1/YKL-40 as marker of circulating tumor cells. Transl. Lung Cancer Res. 4, 287–291 (2015).
pubmed: 26207216
pmcid: 4483474
Xu, C. H., Yu, L. K. & Hao, K. K. Serum YKL-40 level is associated with the chemotherapy response and prognosis of patients with small cell lung cancer. PLoS One 9, e96384 (2014).
pubmed: 24801872
pmcid: 4011792
doi: 10.1371/journal.pone.0096384
Kim, H. R. et al. Levels of YKL-40 in pleural effusions and blood from patients with pulmonary or pleural disease. Cytokine 58, 336–343 (2012).
pubmed: 22480951
doi: 10.1016/j.cyto.2012.03.001
Choi, I. K., Kim, Y. H., Kim, J. S. & Seo, J. H. High serum YKL-40 is a poor prognostic marker in patients with advanced non-small cell lung cancer. Acta Oncol. 49, 861–864 (2010).
pubmed: 20553098
doi: 10.3109/02841861003631503
Junker, N., Johansen, J. S., Andersen, C. B. & Kristjansen, P. E. Expression of YKL-40 by peritumoral macrophages in human small cell lung cancer. Lung Cancer 48, 223–231 (2005).
pubmed: 15829322
doi: 10.1016/j.lungcan.2004.11.011
Johansen, J. S., Drivsholm, L., Price, P. A. & Christensen, I. J. High serum YKL-40 level in patients with small cell lung cancer is related to early death. Lung Cancer 46, 333–340 (2004).
pubmed: 15541818
doi: 10.1016/j.lungcan.2004.05.010
Wang, J., Sheng, Z., Yang, W. & Cai, Y. Elevated serum concentration of Chitinase 3-Like 1 is an independent prognostic biomarker for poor survival in lung cancer patients. Cell. Physiol. Biochem. 38, 461–468 (2016).
pubmed: 26828595
doi: 10.1159/000438643
Jefri, M., Huang, Y. N., Huang, W. C., Tai, C. S. & Chen, W. L. YKL-40 regulated epithelial-mesenchymal transition and migration/invasion enhancement in non-small cell lung cancer. BMC Cancer 15, 590 (2015).
pubmed: 26275425
pmcid: 4537570
doi: 10.1186/s12885-015-1592-3
Wang, X. W., Cai, C. L., Xu, J. M., Jin, H. & Xu, Z. Y. Increased expression of chitinase 3-like 1 is a prognosis marker for non-small cell lung cancer correlated with tumor angiogenesis. Tumour Biol. 36, 901–907 (2015).
pubmed: 25304157
doi: 10.1007/s13277-014-2690-6
Rusak, A., Jablonska, K. & Dziegiel, P. The role of YKL-40 in a cancerous process. Postepy Hig. Med. Dosw . 70, 1286–1299 (2016).
Thom, I. et al. Elevated pretreatment serum concentration of YKL-40-An independent prognostic biomarker for poor survival in patients with metastatic nonsmall cell lung cancer. Cancer 116, 4114–4121 (2010).
pubmed: 20564116
doi: 10.1002/cncr.25196
Coffman, F. D. Chitinase 3-Like-1 (CHI3L1): a putative disease marker at the interface of proteomics and glycomics. Crit. Rev. Clin. Lab. Sci. 45, 531–562 (2008).
pubmed: 19003601
doi: 10.1080/10408360802334743
Johansen, J. S. Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med. Bull. 53, 172–209 (2006).
pubmed: 17087877
Kim, D. H. et al. Regulation of chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis. Nat. Commun. 9, 503 (2018).
pubmed: 29403003
pmcid: 5799380
doi: 10.1038/s41467-017-02731-6
Corradi, M. et al. YKL-40 and mesothelin in the blood of patients with malignant mesothelioma, lung cancer and asbestosis. Anticancer Res. 33, 5517–5524 (2013).
pubmed: 24324091
Lee, C. M. et al. IL-13Ralpha2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses. Nat .Commun. 7, 12752 (2016).
pubmed: 27629921
pmcid: 5027616
doi: 10.1038/ncomms12752
Lee, C. G. et al. Role of breast regression protein 39 (BRP-39)/chitinase 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis. J. Exp. Med. 206, 1149–1166 (2009).
pubmed: 19414556
pmcid: 2715037
doi: 10.1084/jem.20081271
Yang, P. S. et al. Targeting protumor factor chitinase-3-like-1 secreted by Rab37 vesicles for cancer immunotherapy. Theranostics 12, 340–361 (2022).
pubmed: 34987649
pmcid: 8690922
doi: 10.7150/thno.65522
Ma, B. et al. CHI3L1 enhances melanoma lung metastasis via regulation of T cell co-stimulators and CTLA-4/B7 axis. Front. Immunol. 13, 1056397 (2022).
pubmed: 36618349
pmcid: 9812560
doi: 10.3389/fimmu.2022.1056397
Lee, Y. S. et al. A small molecule targeting CHI3L1 inhibits lung metastasis by blocking IL-13Ralpha2-mediated JNK-AP-1 signals. Mol. Oncol. 16, 508–526 (2022).
pubmed: 34758182
doi: 10.1002/1878-0261.13138
Hong, D. E. et al. A natural CHI3L1-targeting compound, ebractenoid F, inhibits lung cancer cell growth and migration and induces apoptosis by blocking CHI3L1/AKT signals. Molecules 28, 329 (2022).
pubmed: 36615523
pmcid: 9822003
doi: 10.3390/molecules28010329
Lauro, S., Onesti, C. E., Righini, R. & Marchetti, P. The use of bevacizumab in non-small cell lung cancer: an update. Anticancer Res. 34, 1537–1545 (2014).
pubmed: 24692680
Uprety, D. Clinical utility of ramucirumab in non-small-cell lung cancer. Biologics 13, 133–137 (2019).
pubmed: 31413541
pmcid: 6659776
Zhang, Y. et al. Tumor-penetration and antitumor efficacy of cetuximab are enhanced by co-administered iRGD in a murine model of human NSCLC. Oncol. Lett. 12, 3241–3249 (2016).
pubmed: 27899989
pmcid: 5103927
doi: 10.3892/ol.2016.5081
Agrawal, S., Feng, Y., Roy, A., Kollia, G. & Lestini, B. Nivolumab dose selection: challenges, opportunities, and lessons learned for cancer immunotherapy. J. Immunother. Cancer 4, 72 (2016).
pubmed: 27879974
pmcid: 5109842
doi: 10.1186/s40425-016-0177-2
Low, J. L. et al. Low-dose pembrolizumab in the treatment of advanced non-small cell lung cancer. Int. J .Cancer 149, 169–176 (2021).
pubmed: 33634869
pmcid: 9545741
doi: 10.1002/ijc.33534
Bao, J. et al. Serum CHI3L1 as a biomarker for non-invasive diagnosis of liver fibrosis. Discov. Med. 33, 41–49 (2022).
pubmed: 36274212
Huang, W. S. et al. Correlation of Chitinase 3-Like 1 single nucleotide polymorphisms with hepatocellular carcinoma in Taiwan. Int. J. Med. Sci. 14, 136–142 (2017).
pubmed: 28260989
pmcid: 5332842
doi: 10.7150/ijms.17754
Mangoud, N. O. M., Ali, S. A., El Kassas, M. & Soror, S. H. Chitinase 3-like-1, Tolloid-like protein 1, and intergenic gene polymorphisms are predictors for hepatocellular carcinoma development after hepatitis C virus eradication by direct-acting antivirals. IUBMB Life 73, 474–482 (2021).
pubmed: 33347699
doi: 10.1002/iub.2444
Peltonen, R. et al. Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases. PLoS One 15, e0236569 (2020).
pubmed: 32756596
pmcid: 7406016
doi: 10.1371/journal.pone.0236569
Wang, S. et al. Diagnostic and prognostic value of serum Chitinase 3-like protein 1 in hepatocellular carcinoma. J. Clin. Lab. Anal. 36, e24234 (2022).
pubmed: 35034385
pmcid: 8841184
doi: 10.1002/jcla.24234
Qiu, Q. C. et al. CHI3L1 promotes tumor progression by activating TGF-beta signaling pathway in hepatocellular carcinoma. Sci. Rep. 8, 15029 (2018).
pubmed: 30301907
pmcid: 6177412
doi: 10.1038/s41598-018-33239-8
Lu, D. et al. Multi-omics profiling reveals Chitinase-3-like protein 1 as a key mediator in the crosstalk between sarcopenia and liver cancer. Redox Biol. 58, 102538 (2022).
pubmed: 36417796
pmcid: 9682348
doi: 10.1016/j.redox.2022.102538
Shantha Kumara, H. M. et al. Plasma chitinase 3-like 1 is persistently elevated during first month after minimally invasive colorectal cancer resection. World J. Gastrointest. Oncol. 8, 607–614 (2016).
pubmed: 27574553
pmcid: 4980651
doi: 10.4251/wjgo.v8.i8.607
Eldaly, M. N., Metwally, F. M., Shousha, W. G., El-Saiid, A. S., & Ramadan, S.S. Clinical potentials of miR-576-3p, miR-613, NDRG2 and YKL40 in colorectal cancer patients. Asian Pac. J. Cancer Prev. 21, 1689–1695 (2020).
pubmed: 32592365
pmcid: 7568881
doi: 10.31557/APJCP.2020.21.6.1689
Kawada, M. et al. Chitinase 3-like 1 promotes macrophage recruitment and angiogenesis in colorectal cancer. Oncogene 31, 3111–3123 (2012).
pubmed: 22056877
doi: 10.1038/onc.2011.498
Watanabe, K. et al. Chitinase 3-like 1 secreted from cancer-associated fibroblasts promotes tumor angiogenesis via interleukin-8 secretion in colorectal cancer. Int. J. Oncol. 60, 3 (2022).
pubmed: 34913066
doi: 10.3892/ijo.2021.5293
Liu, K., Jin, M., Ye, S. & Yan, S. CHI3L1 promotes proliferation and improves sensitivity to cetuximab in colon cancer cells by down-regulating p53. J. Clin. Lab. Anal. 34, e23026 (2020).
pubmed: 31536166
doi: 10.1002/jcla.23026
Yang, M. S. et al. Chitinase-3-like 1 (CHI3L1) gene and schizophrenia: genetic association and a potential functional mechanism. Biol. Psychiatry 64, 98–103 (2008).
pubmed: 18281018
doi: 10.1016/j.biopsych.2007.12.012
Lananna, B. V. et al. Chi3l1/YKL-40 is controlled by the astrocyte circadian clock and regulates neuroinflammation and Alzheimer’s disease pathogenesis. Sci. Transl. Med. 12, eaax3519 (2020).
pubmed: 33328329
pmcid: 7808313
doi: 10.1126/scitranslmed.aax3519
Craig-Schapiro, R. et al. YKL-40: a novel prognostic fluid biomarker for preclinical Alzheimer’s disease. Biol. Psychiatry 68, 903–912 (2010).
pubmed: 21035623
pmcid: 3011944
doi: 10.1016/j.biopsych.2010.08.025
Choi, J., Lee, H.-W. & Suk, K. Plasma level of chitinase 3-like 1 protein increases in patients with early Alzheimer’s disease. J. Neurol. 258, 2181–2185 (2011).
pubmed: 21562723
doi: 10.1007/s00415-011-6087-9
Sanfilippo, C., Malaguarnera, L. & Di Rosa, M. Chitinase expression in Alzheimer’s disease and non-demented brains regions. J. Neurol. Sci. 369, 242–249 (2016).
pubmed: 27653898
doi: 10.1016/j.jns.2016.08.029
Rakic, S. et al. Systemic infection modifies the neuroinflammatory response in late stage Alzheimer’s disease. Acta Neuropathol. Commun. 6, 1–13 (2018).
doi: 10.1186/s40478-018-0592-3
Sanfilippo, C. et al. Sex-dependent neuro-deconvolution analysis of Alzheimer’s disease brain transcriptomes according to CHI3L1 expression levels. J. Neuroimmunol. 373, 577977 (2022).
pubmed: 36228382
doi: 10.1016/j.jneuroim.2022.577977
Sanfilippo, C. et al. CHI3L1 and CHI3L2 overexpression in motor cortex and spinal cord of sALS patients. Mol. Cell. Neurosci. 85, 162–169 (2017).
pubmed: 28989002
doi: 10.1016/j.mcn.2017.10.001
Long, X. et al. Hippocampal YKL-40 expression in rats after status epilepticus. Epilepsy Res. 125, 52–57 (2016).
pubmed: 27393917
doi: 10.1016/j.eplepsyres.2016.05.014
Carter, S. F. et al. Astrocyte biomarkers in Alzheimer’s disease. Trends Mol. Med. 25, 77–95 (2019).
pubmed: 30611668
doi: 10.1016/j.molmed.2018.11.006
Teitsdottir, U. D. et al. Cerebrospinal fluid C18 ceramide associates with markers of Alzheimer’s disease and inflammation at the pre-and early stages of dementia. J. Alzheimers Dis. 81, 231–244 (2021).
pubmed: 33814423
pmcid: 8203241
doi: 10.3233/JAD-200964
Watabe-Rudolph, M. et al. Chitinase enzyme activity in CSF is a powerful biomarker of Alzheimer disease. Neurology 78, 569–577 (2012).
pubmed: 22323746
doi: 10.1212/WNL.0b013e318247caa1
Groblewska, M. & Mroczko, B. YKL-40 as a potential biomarker and a possible target in therapeutic strategies of Alzheimer’s disease. Curr. Neuropharmacol. 15, 906–917 (2017).
pubmed: 28183245
pmcid: 5652033
Bonneh‐Barkay, D. et al. Astrocyte and macrophage regulation of YKL‐40 expression and cellular response in neuroinflammation. Brain Pathol. 22, 530–546 (2012).
pubmed: 22074331
doi: 10.1111/j.1750-3639.2011.00550.x
Moreno-Rodriguez, M., Perez, S. E., Nadeem, M., Malek-Ahmadi, M. & Mufson, E. J. Frontal cortex chitinase and pentraxin neuroinflammatory alterations during the progression of Alzheimer’s disease. J. Neuroinflamm. 17, 1–15 (2020).
doi: 10.1186/s12974-020-1723-x
Naka, K. K. et al. Association of vascular indices with novel circulating biomarkers as prognostic factors for cardiovascular complications in patients with type 2 diabetes mellitus. Clin. Biochem. 53, 31–37 (2018).
pubmed: 29288632
doi: 10.1016/j.clinbiochem.2017.12.010
Molina-Martínez, P. et al. Microglial hyperreactivity evolved to immunosuppression in the hippocampus of a mouse model of accelerated aging and Alzheimer’s Disease traits. Front. Aging Neurosci. 12, 622360 (2021).
pubmed: 33584248
pmcid: 7875867
doi: 10.3389/fnagi.2020.622360
Chen, C.-H. et al. Increased NF-κB signalling up-regulates BACE1 expression and its therapeutic potential in Alzheimer’s disease. Int. J. Neuropsychopharmacol. 15, 77–90 (2012).
pubmed: 21329555
doi: 10.1017/S1461145711000149
Rolova, T. et al. Deletion of nuclear factor kappa B p50 subunit decreases inflammatory response and mildly protects neurons from transient forebrain ischemia-induced damage. Aging Dis. 7, 450 (2016).
pubmed: 27493832
doi: 10.14336/AD.2015.1123
Snow, W. M. & Albensi, B. C. Neuronal gene targets of NF-κB and their dysregulation in Alzheimer’s disease. Front. Mol. Neurosci. 9, 118 (2016).
pubmed: 27881951
pmcid: 5101203
doi: 10.3389/fnmol.2016.00118
Gispert, J. D. et al. The APOE ε4 genotype modulates CSF YKL-40 levels and their structural brain correlates in the continuum of Alzheimer’s disease but not those of sTREM2. Alzheimers Dement 6, 50–59 (2017).
Zhang, H. et al. Cerebrospinal fluid phosphorylated tau, visinin-like protein-1, and chitinase-3-like protein 1 in mild cognitive impairment and Alzheimer’s disease. Alzheimers Dement 7, 1–12 (2018).
Llorens, F. et al. YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias. Int. J. Mol. Sci. 12, 1–21 (2017).
Jung, Y. Y. et al. Atherosclerosis is exacerbated by chitinase-3-like-1 in amyloid precursor protein transgenic mice. Theranostics 8, 749–766 (2018).
pubmed: 29344304
pmcid: 5771091
doi: 10.7150/thno.20183
Choi, J. Y. et al. K284-6111 prevents the amyloid beta-induced neuroinflammation and impairment of recognition memory through inhibition of NF-κB-mediated CHI3L1 expression. J. Neuroinflamm. 15, 1–13 (2018).
doi: 10.1186/s12974-018-1269-3
Ham, H. J. et al. K284-6111 alleviates memory impairment and neuroinflammation in Tg2576 mice by inhibition of Chitinase-3-like 1 regulating ERK-dependent PTX3 pathway. J. Neuroinflamm. 17, 1–16 (2020).
doi: 10.1186/s12974-020-02022-w
Chung, C., Tallerico, T. & Seeman, P. Schizophrenia hippocampus has elevated expression of chondrex glycoprotein gene. Synapse 50, 29–34 (2003).
pubmed: 12872291
doi: 10.1002/syn.10228
Zhao, X. et al. Functional variants in the promoter region of chitinase 3–like 1 (CHI3L1) and susceptibility to schizophrenia. Am. J. Hum. Genet. 80, 12–18 (2007).
pubmed: 17160890
doi: 10.1086/510438
Ohi, K. et al. The chitinase 3-like 1 gene and schizophrenia: Evidence from a multi-center case–control study and meta-analysis. Schizophr. Res. 116, 126–132 (2010).
pubmed: 20051317
doi: 10.1016/j.schres.2009.12.002
Gomez, J. L. et al. Genetic variation in chitinase 3-like 1 (CHI3L1) contributes to asthma severity and airway expression of YKL-40. J. Allergy Clin. Immunol. 136, 51–58.e10 (2015).
pubmed: 25592985
pmcid: 4494869
doi: 10.1016/j.jaci.2014.11.027
Yamada, K. et al. Failure to confirm genetic association of the CHI3L1 gene with schizophrenia in Japanese and Chinese populations. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150, 508–514 (2009).
doi: 10.1002/ajmg.b.30847
Kwak, E. J. et al. Chitinase 3-like 1 drives allergic skin inflammation via Th2 immunity and M2 macrophage activation. Clin. Exp. Allergy 49, 1464–1474 (2019).
pubmed: 31397016
doi: 10.1111/cea.13478
Libreros, S. et al. Allergen induced pulmonary inflammation enhances mammary tumor growth and metastasis: Role of CHI3L1. J. Leukoc. Biol. 97, 929–940 (2015).
pubmed: 25765679
doi: 10.1189/jlb.3A0214-114RR
Müller, N. et al. Impaired monocyte activation in schizophrenia. Front. Neurosci. 198, 341–346 (2012).
Khandaker, G. M. & Dantzer, R. Is there a role for immune-to-brain communication in schizophrenia? Psychopharmacology 233, 1559–1573 (2016).
pubmed: 26037944
doi: 10.1007/s00213-015-3975-1
Upthegrove, R. & Khandaker, G. M. Cytokines, oxidative stress and cellular markers of inflammation in schizophrenia. Curr. Top Behav. Neurosci. 44, 49–66 (2020).
pubmed: 31115797
doi: 10.1007/7854_2018_88
Emamian, E. S., Hall, D., Birnbaum, M. J., Karayiorgou, M. & Gogos, J. A. Convergent evidence for impaired AKT1-GSK3β signaling in schizophrenia. Nat. Genet. 36, 131–137 (2004).
pubmed: 14745448
doi: 10.1038/ng1296
Zhao, T., Su, Z., Li, Y., Zhang, X. & You, Q. Chitinase-3 like-protein-1 function and its role in diseases. Signal. Transduct. Target Ther. 5, 201 (2020).
pubmed: 32929074
pmcid: 7490424
doi: 10.1038/s41392-020-00303-7
Lencz, T. et al. Converging evidence for a pseudoautosomal cytokine receptor gene locus in schizophrenia. Mol. Psychiatry 12, 572–580 (2007).
pubmed: 17522711
doi: 10.1038/sj.mp.4001983
Arion, D., Unger, T., Lewis, D. A., Levitt, P. & Mirnics, K. Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol. Psychiatry 62, 711–721 (2007).
pubmed: 17568569
pmcid: 2080683
doi: 10.1016/j.biopsych.2006.12.021
Hwang, Y. et al. Gene expression profiling by mRNA sequencing reveals increased expression of immune/inflammation-related genes in the hippocampus of individuals with schizophrenia. Transl. Psychiatry 3, e321–e321 (2013).
pubmed: 24169640
pmcid: 3818014
doi: 10.1038/tp.2013.94
Orhan, F. et al. Increased number of monocytes and plasma levels of MCP‐1 and YKL‐40 in first‐episode psychosis. Acta Psychiatr. Scand. 138, 432–440 (2018).
pubmed: 30132802
doi: 10.1111/acps.12944
Yeo, I. J. et al. Overexpression of transmembrane TNFalpha in brain endothelial cells induces schizophrenia-relevant behaviors. Mol. Psychiatry 28, 843–855 (2023).
pubmed: 36333582
doi: 10.1038/s41380-022-01846-7
Piñero, J. et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res. 45, D833–D839 (2017).
pubmed: 27924018
doi: 10.1093/nar/gkw943
Hall, S. et al. Cerebrospinal fluid concentrations of inflammatory markers in Parkinson’s disease and atypical parkinsonian disorders. Sci. Rep. 8, 13276 (2018).
pubmed: 30185816
pmcid: 6125576
doi: 10.1038/s41598-018-31517-z
Aarsland, D. et al. Parkinson disease-associated cognitive impairment. Nat. Rev. Dis. Primers 7, 47 (2021).
pubmed: 34210995
doi: 10.1038/s41572-021-00280-3
Anwar, M. M. & Fathi, M. H. Early approaches of YKL-40 as a biomarker and therapeutic target for Parkinson’s disease. Neurodegener Dis. Manag. 3, 85–99 (2023).
doi: 10.2217/nmt-2022-0010
Vu, L. et al. Cross-sectional and longitudinal measures of chitinase proteins in amyotrophic lateral sclerosis and expression of CHI3L1 in activated astrocytes. J. Neurol. Neurosurg. Psychiatry 91, 350–358 (2020).
pubmed: 31937582
doi: 10.1136/jnnp-2019-321916
Vinther-Jensen, T. et al. Selected CSF biomarkers indicate no evidence of early neuroinflammation in Huntington disease. Neurol. Neuroimmunol. Neuroinflamm. 3, e287 (2016).
pubmed: 27734023
pmcid: 5042104
doi: 10.1212/NXI.0000000000000287
Quintana, E. et al. Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3‐like 1 and neurofilament light chain. Eur. J. Neurol. 25, 1189–1191 (2018).
pubmed: 29797629
doi: 10.1111/ene.13687
Floro, S. et al. Role of Chitinase 3–like 1 as a biomarker in multiple sclerosis: a systematic review and meta-analysis. Neurol. Neuroimmunol. Neuroinflamm. 9, e1164 (2022).
pubmed: 35534236
pmcid: 9128043
doi: 10.1212/NXI.0000000000001164
Cong, S., Xiang, C., Wang, H. & Cong, S. Diagnostic utility of fluid biomarkers in multiple system atrophy: a systematic review and meta-analysis. J. Neurol. 268, 2703–2712 (2021).
pubmed: 32162061
doi: 10.1007/s00415-020-09781-9
Autar, K. et al. ASNTR Abstracts 2021. Cell Transplant 30, 1–25 (2021).
Langenbruch, L., Wiendl, H., Groß, C. & Kovac, S. Diagnostic utility of cerebrospinal fluid (CSF) findings in seizures and epilepsy with and without autoimmune-associated disease. Seizure 91, 233–243 (2021).
pubmed: 34233238
doi: 10.1016/j.seizure.2021.06.030
Gimbrone, M. A. Jr. & Garcia-Cardena, G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ. Res. 118, 620–636 (2016).
pubmed: 26892962
pmcid: 4762052
doi: 10.1161/CIRCRESAHA.115.306301
Basatemur, G. L., Jorgensen, H. F., Clarke, M. C. H., Bennett, M. R. & Mallat, Z. Vascular smooth muscle cells in atherosclerosis. Nat. Rev. Cardiol. 16, 727–744 (2019).
pubmed: 31243391
doi: 10.1038/s41569-019-0227-9
Dong, Y., Zhang, Y., Yang, X., Yan, C. & Feng, Y. Recent insights into neutrophil extracellular traps in cardiovascular diseases. J. Clin. Med. 11, 6662 (2022).
pubmed: 36431139
pmcid: 9698501
doi: 10.3390/jcm11226662
Moroni, F., Ammirati, E., Norata, G. D., Magnoni, M. & Camici, P. G. The role of monocytes and macrophages in human atherosclerosis, plaque neoangiogenesis, and atherothrombosis. Mediators Inflamm. 2019, 7434376 (2019).
pubmed: 31089324
pmcid: 6476044
doi: 10.1155/2019/7434376
Boot, R. G. et al. Strong induction of members of the chitinase family of proteins in atherosclerosis: chitotriosidase and human cartilage gp-39 expressed in lesion macrophages. Arterioscler Thromb Vasc. Biol. 19, 687–694 (1999).
pubmed: 10073974
doi: 10.1161/01.ATV.19.3.687
Xu, T. et al. YKL-40 level and hypertension incidence: a population-based nested case-control study in China. J. Am. Heart Assoc. 5, e004534 (2016).
pubmed: 27815265
pmcid: 5210351
doi: 10.1161/JAHA.116.004534
Malyszko, J., Koc-Zorawska, E. & Malyszko, J. YKL-40, a marker of cardiovascular disease and endothelial dysfunction, in kidney transplant recipients. Transplant Proc. 46, 2651–2653 (2014).
pubmed: 25380887
doi: 10.1016/j.transproceed.2014.09.017
Erfan, G. et al. Serum YKL-40: a potential biomarker for psoriasis or endothelial dysfunction in psoriasis? Mol. Cell. Biochem. 400, 207–212 (2015).
pubmed: 25421412
doi: 10.1007/s11010-014-2277-y
Jafari, B. & Mohsenin, V. Chitinase-3-like protein-1 (YKL-40) as a marker of endothelial dysfunction in obstructive sleep apnea. Sleep Med. 25, 87–92 (2016).
pubmed: 27823723
doi: 10.1016/j.sleep.2016.08.001
Keskin, G. S. et al. Relationship between plasma YKL-40 levels and endothelial dysfunction in chronic kidney disease. Turk. J. Med. Sci. 49, 139–146 (2019).
pubmed: 30763987
pmcid: 7350791
Kocyigit, I. et al. The serum YKL-40 level is associated with vascular injury and predicts proteinuria in nephrotic syndrome patients. J. Atheroscler. Thromb. 22, 257–264 (2015).
pubmed: 25253160
doi: 10.5551/jat.26385
Zheng, J. L. et al. Increased serum YKL-40 and C-reactive protein levels are associated with angiographic lesion progression in patients with coronary artery disease. Atherosclerosis 210, 590–595 (2010).
pubmed: 20056225
doi: 10.1016/j.atherosclerosis.2009.12.016
Michelsen, A. E. et al. Increased YKL-40 expression in patients with carotid atherosclerosis. Atherosclerosis 211, 589–595 (2010).
pubmed: 20347092
doi: 10.1016/j.atherosclerosis.2010.02.035
Jiao, Y. et al. Early identification of carotid vulnerable plaque in asymptomatic patients. BMC Cardiovasc. Disord. 20, 429 (2020).
pubmed: 33003997
pmcid: 7528473
doi: 10.1186/s12872-020-01709-5
Wu, S. et al. Circulating YKL-40 level, but not CHI3L1 gene variants, is associated with atherosclerosis-related quantitative traits and the risk of peripheral artery disease. Int. J. Mol. Sci. 15, 22421–22437 (2014).
pubmed: 25486056
pmcid: 4284717
doi: 10.3390/ijms151222421
Hobaus, C. et al. YKL-40 levels increase with declining ankle-brachial index and are associated with long-term cardiovascular mortality in peripheral arterial disease patients. Atherosclerosis 274, 152–156 (2018).
pubmed: 29783062
doi: 10.1016/j.atherosclerosis.2018.05.006
Aguilera, E. et al. Relationship of YKL-40 and adiponectin and subclinical atherosclerosis in asymptomatic patients with type 1 diabetes mellitus from a European Mediterranean population. Cardiovasc. Diabetol. 14, 121 (2015).
pubmed: 26382922
pmcid: 4574547
doi: 10.1186/s12933-015-0287-z
Bakirci, E. M. et al. Serum YKL-40/chitinase 3-like protein 1 level is an independent predictor of atherosclerosis development in patients with obstructive sleep apnea syndrome. Turk Kardiyol Dern. Ars. 43, 333–339 (2015).
pubmed: 26142786
Kulkarni, N. B., Ganu, M. U., Godbole, S. G. & Deo, S. S. Assessment of potential biomarkers of atherosclerosis in Indian patients with type 2 diabetes mellitus. Indian J. Med. Res. 147, 169–176 (2018).
pubmed: 29806605
pmcid: 5991114
doi: 10.4103/ijmr.IJMR_852_16
Kwon, Y. et al. Serum YKL-40 levels are associated with the atherogenic index of plasma in children. Mediators Inflamm. 2020, 8713908 (2020).
pubmed: 33061832
pmcid: 7533750
doi: 10.1155/2020/8713908
Yamada, K., Hyodo, T., Urabe, S., Haga, S. & Hosaka, T. Serum YKL-40 level is associated with Geriatric Nutritional Risk Index (GNRI) and γ-GTP in hemodialysis patients. J. Med. Investig. 69, 101–106 (2022).
doi: 10.2152/jmi.69.101
Chen, X. L. et al. Serum YKL-40, a prognostic marker in patients with large-artery atherosclerotic stroke. Acta Neurol. Scand. 136, 97–102 (2017).
pubmed: 27650381
doi: 10.1111/ane.12688
Akboga, M. K., Yalcin, R., Sahinarslan, A., Yilmaz Demirtas, C. & Abaci, A. Effect of serum YKL-40 on coronary collateral development and SYNTAX score in stable coronary artery disease. Int. J. Cardiol. 224, 323–327 (2016).
pubmed: 27668705
doi: 10.1016/j.ijcard.2016.09.042
Sciborski, K. et al. Plasma YKL-40 levels correlate with the severity of coronary atherosclerosis assessed with the SYNTAX score.Pol. Arch. Intern. Med. 128, 644–648 (2018).
pubmed: 30303489
Schroder, J. et al. Prognosis and reclassification by YKL-40 in stable coronary artery disease. J. Am. Heart Assoc. 9, e014634 (2020).
pubmed: 32114892
pmcid: 7335588
doi: 10.1161/JAHA.119.014634
Przybyłowski, P. et al. YKL-40, a novel marker of cardiovascular complications, is related to kidney function in heart transplant recipients. Transplant Proc. 46, 2860–2863 (2014).
pubmed: 25380936
doi: 10.1016/j.transproceed.2014.09.042
Laucyte-Cibulskiene, A. et al. Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality. Biol. Sex Differ. 12, 50 (2021).
pubmed: 34526107
pmcid: 8444580
doi: 10.1186/s13293-021-00393-0
Chen, G. et al. Elevated plasma YKL-40 as a prognostic indicator in patients with idiopathic pulmonary arterial hypertension. Respirology 19, 608–615 (2014).
pubmed: 24689969
doi: 10.1111/resp.12283
Masajtis-Zagajewska, A., Majer, J. & Nowicki, M. Effect of moxonidine and amlodipine on serum YKL-40, plasma lipids and insulin sensitivity in insulin-resistant hypertensive patients-a randomized, crossover trial. Hypertens. Res. 33, 348–353 (2010).
pubmed: 20139920
doi: 10.1038/hr.2010.6
Mathiasen, A. B. et al. Plasma YKL-40 in relation to the degree of coronary artery disease in patients with stable ischemic heart disease. Scand. J. Clin. Lab. Investig. 71, 439–447 (2011).
doi: 10.3109/00365513.2011.586470
Qi, R. et al. Effect of laparoscopic splenectomy on portal vein thrombosis and serum YKL-40 in patients with cirrhotic portal hypertension. Ann. Hepatol. 18, 898–901 (2019).
pubmed: 31427175
doi: 10.1016/j.aohep.2019.06.009
Sun, X. et al. Chitinase 3 like 1 contributes to the development of pulmonary vascular remodeling in pulmonary hypertension. JCI Insight 7, e159578 (2022).
pubmed: 35951428
pmcid: 9675485
doi: 10.1172/jci.insight.159578
Xing, Y., Guo, J., Gai, L., Liu, B. & Luo, D. Serum YKL-40 is associated with the severity of coronary artery disease and hypertension. Asian J. Surg. 43, 1121–1122 (2020).
pubmed: 33023792
doi: 10.1016/j.asjsur.2020.08.016
Xu, T. et al. YKL-40 is a novel biomarker for predicting hypertension incidence among prehypertensive subjects: a population-based nested case-control study in China. Clin. Chim. Acta 472, 146–150 (2017).
pubmed: 28797750
doi: 10.1016/j.cca.2017.08.003
Cetin, M. et al. Elevated serum YKL40 level is a predictor of MACE during the long-term follow up in hypertensive patients. Clin. Exp. Hypertens. 42, 271–274 (2020).
pubmed: 31204510
doi: 10.1080/10641963.2019.1632342
Li, K., Chen, Z., Qin, Y. & Wei, Y. X. Plasm YKL-40 levels are associated with hypertension in patients with obstructive sleep apnea. Biomed. Res. Int. 2019, 5193597 (2019).
pubmed: 31001555
pmcid: 6436335
Karalilova, R. et al. Serum YKL-40 and IL-6 levels correlate with ultrasound findings of articular and periarticular involvement in patients with systemic sclerosis. Rheumatol. Int. 39, 1841–1848 (2019).
pubmed: 31375891
doi: 10.1007/s00296-019-04402-9
Nordenbaek, C. et al. High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement. Scand. J. Rheumatol. 34, 293–297 (2005).
pubmed: 16195162
doi: 10.1080/03009740510018598
Furukawa, T. et al. Relationship between YKL-40 and pulmonary arterial hypertension in systemic sclerosis. Mod. Rheumatol. 29, 476–483 (2019).
pubmed: 29788800
doi: 10.1080/14397595.2018.1480256
Konig, K. et al. BNP, troponin I, and YKL-40 as screening markers in extremely preterm infants at risk for pulmonary hypertension associated with bronchopulmonary dysplasia. Am. J. Physiol. Lung Cell. Mol. Physiol. 311, L1076–L1081 (2016).
pubmed: 27760764
doi: 10.1152/ajplung.00344.2016
Zhou, Y., Meng, L. J. & Wang, J. Changes in serum human cartilage glycoprotein-39 and high-mobility group box 1 in preterm infants with bronchopulmonary dysplasia. Zhongguo Dang Dai Er Ke Za Zhi 22, 334–338 (2020).
pubmed: 32312371
Bilim, O. et al. Serum YKL-40 predicts adverse clinical outcomes in patients with chronic heart failure. J. Card Fail 16, 873–879 (2010).
pubmed: 21055651
doi: 10.1016/j.cardfail.2010.05.029
Ma, W. H. et al. Association between human cartilage glycoprotein 39 (YKL-40) and arterial stiffness in essential hypertension. BMC Cardiovasc. Disord. 12, 35 (2012).
pubmed: 22642467
pmcid: 3438025
doi: 10.1186/1471-2261-12-35
Ma, C. Y. et al. Change of inflammatory factors in patients with acute coronary syndrome. Chin Med. J. 131, 1444–1449 (2018).
pubmed: 29893361
pmcid: 6006811
doi: 10.4103/0366-6999.233953
Harutyunyan, M. et al. The inflammatory biomarker YKL-40 as a new prognostic marker for all-cause mortality in patients with heart failure. Immunobiology 217, 652–656 (2012).
pubmed: 22209156
doi: 10.1016/j.imbio.2011.11.003
Arain, F. et al. YKL-40 (Chitinase-3-Like Protein 1) Serum Levels in Aortic Stenosis. Circ. Heart Fail 13, e006643 (2020).
pubmed: 32962417
doi: 10.1161/CIRCHEARTFAILURE.119.006643
Mathiasen, A. B., Henningsen, K. M., Harutyunyan, M. J., Mygind, N. D. & Kastrup, J. YKL-40: a new biomarker in cardiovascular disease? Biomark. Med. 4, 591–600 (2010).
pubmed: 20701447
doi: 10.2217/bmm.10.58
Bakirci, E. M. et al. New inflammatory markers for prediction of non-dipper blood pressure pattern in patients with essential hypertension: serum YKL-40/Chitinase 3-like protein 1 levels and echocardiographic epicardial adipose tissue thickness. Clin. Exp. Hypertens. 37, 505–510 (2015).
pubmed: 25919569
doi: 10.3109/10641963.2015.1013122
Vergadi, E. et al. Early macrophage recruitment and alternative activation are critical for the later development of hypoxia-induced pulmonary hypertension. Circulation 123, 1986–1995 (2011).
pubmed: 21518986
pmcid: 3125055
doi: 10.1161/CIRCULATIONAHA.110.978627
Waki, H., Gouraud, S. S., Maeda, M. & Paton, J. F. Gene expression profiles of major cytokines in the nucleus tractus solitarii of the spontaneously hypertensive rat. Auton. Neurosci. 142, 40–44 (2008).
pubmed: 18703386
doi: 10.1016/j.autneu.2008.07.001
Ross, R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801–809 (1993).
pubmed: 8479518
doi: 10.1038/362801a0
Libby, P., Ridker, P. M. & Maseri, A. Inflammation and atherosclerosis. Circulation 105, 1135–1143 (2002).
pubmed: 11877368
doi: 10.1161/hc0902.104353
Cines, D. B. et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 91, 3527–3561 (1998).
pubmed: 9572988
Galley, H. F. & Webster, N. R. Physiology of the endothelium. Br. J. Anaesth. 93, 105–113 (2004).
pubmed: 15121728
doi: 10.1093/bja/aeh163
Sima, A. V., Stancu, C. S. & Simionescu, M. Vascular endothelium in atherosclerosis. Cell Tissue Res. 335, 191–203 (2009).
pubmed: 18797930
doi: 10.1007/s00441-008-0678-5
Deanfield, J. E., Halcox, J. P. & Rabelink, T. J. Endothelial function and dysfunction: testing and clinical relevance. Circulation 115, 1285–1295 (2007).
pubmed: 17353456
doi: 10.1161/CIRCULATIONAHA.106.652859
Shackelton, L. M., Mann, D. M. & Millis, A. J. Identification of a 38-kDa heparin-binding glycoprotein (gp38k) in differentiating vascular smooth muscle cells as a member of a group of proteins associated with tissue remodeling. J. Biol. Chem. 270, 13076–13083 (1995).
pubmed: 7768902
doi: 10.1074/jbc.270.22.13076
Malinda, K. M., Ponce, L., Kleinman, H. K., Shackelton, L. M. & Millis, A. J. Gp38k, a protein synthesized by vascular smooth muscle cells, stimulates directional migration of human umbilical vein endothelial cells. Exp. Cell. Res. 250, 168–173 (1999).
pubmed: 10388530
doi: 10.1006/excr.1999.4511
Jung, T. W. et al. Chitinase-3-like protein 1 ameliorates atherosclerotic responses via PPARδ-mediated suppression of inflammation and ER stress. J. Cell. Biochem. 119, 6795–6805 (2018).
pubmed: 29737637
doi: 10.1002/jcb.26873
Steenbakkers, P. G. et al. Localization of MHC class II/human cartilage glycoprotein-39 complexes in synovia of rheumatoid arthritis patients using complex-specific monoclonal antibodies. J. Immunol. 170, 5719–5727 (2003).
pubmed: 12759455
doi: 10.4049/jimmunol.170.11.5719
van Bilsen, J. H. et al. Functional regulatory immune responses against human cartilage glycoprotein-39 in health vs. proinflammatory responses in rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 101, 17180–17185 (2004).
pubmed: 15569925
pmcid: 535402
doi: 10.1073/pnas.0407704101
van Lierop, M. J. et al. Endogenous HLA-DR-restricted presentation of the cartilage antigens human cartilage gp-39 and melanoma inhibitory activity in the inflamed rheumatoid joint. Arthritis. Rheum. 56, 2150–2159 (2007).
pubmed: 17599744
doi: 10.1002/art.22651
Vos, K. et al. Raised human cartilage glycoprotein-39 plasma levels in patients with rheumatoid arthritis and other inflammatory conditions. Ann. Rheum. Dis 59, 544–548 (2000).
pubmed: 10873965
pmcid: 1753190
doi: 10.1136/ard.59.7.544
Tsark, E. C. et al. Differential MHC class II-mediated presentation of rheumatoid arthritis autoantigens by human dendritic cells and macrophages. J. Immunol. 169, 6625–6633 (2002).
pubmed: 12444176
doi: 10.4049/jimmunol.169.11.6625
Vos, K. et al. Cellular immune response to human cartilage glycoprotein-39 (HC gp-39)-derived peptides in rheumatoid arthritis and other inflammatory conditions. Rheumatology 39, 1326–1331 (2000).
pubmed: 11136874
doi: 10.1093/rheumatology/39.12.1326
Johansen, J. S., Jensen, H. S. & Price, P. A. A new biochemical marker for joint injury. Analysis of YKL-40 in serum and synovial fluid. Br. J. Rheumatol. 32, 949–955 (1993).
pubmed: 8220933
doi: 10.1093/rheumatology/32.11.949
Volck, B. et al. Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology. Osteoarthritis Cartilage 9, 203–214 (2001).
pubmed: 11300743
doi: 10.1053/joca.2000.0377
Baeten, D. et al. Detection of major histocompatibility complex/human cartilage gp-39 complexes in rheumatoid arthritis synovitis as a specific and independent histologic marker. Arthritis Rheum. 50, 444–451 (2004).
pubmed: 14872486
doi: 10.1002/art.20012
Cope, A. P. et al. T cell responses to a human cartilage autoantigen in the context of rheumatoid arthritis-associated and nonassociated HLA-DR4 alleles. Arthritis Rheum. 42, 1497–1507 (1999).
pubmed: 10403279
doi: 10.1002/1529-0131(199907)42:7<1497::AID-ANR25>3.0.CO;2-#
Vaananen, T. et al. Glycoprotein YKL-40: A potential biomarker of disease activity in rheumatoid arthritis during intensive treatment with csDMARDs and infliximab. Evidence from the randomised controlled NEO-RACo trial. PLoS One 12, e0183294 (2017).
pubmed: 28841649
pmcid: 5571914
doi: 10.1371/journal.pone.0183294
Houseman, M. et al. Baseline serum MMP-3 levels in patients with Rheumatoid Arthritis are still independently predictive of radiographic progression in a longitudinal observational cohort at 8 years follow up. Arthritis Res. Ther. 14, R30 (2012).
pubmed: 22314025
pmcid: 3392825
doi: 10.1186/ar3734
Mottonen, T. et al. Comparison of combination therapy with single-drug therapy in early rheumatoid arthritis: a randomised trial. FIN-RACo trial group. Lancet 353, 1568–1573 (1999).
pubmed: 10334255
doi: 10.1016/S0140-6736(98)08513-4
Stevens, A. L., Wishnok, J. S., Chai, D. H., Grodzinsky, A. J. & Tannenbaum, S. R. A sodium dodecyl sulfate-polyacrylamide gel electrophoresis-liquid chromatography tandem mass spectrometry analysis of bovine cartilage tissue response to mechanical compression injury and the inflammatory cytokines tumor necrosis factor alpha and interleukin-1beta. Arthritis Rheum. 58, 489–500 (2008).
pubmed: 18240213
doi: 10.1002/art.23120
Jin, T. et al. The Role of MicroRNA, miR-24, and Its Target CHI3L1 in Osteomyelitis Caused by Staphylococcus aureus. J. Cell. Biochem. 116, 2804–2813 (2015).
pubmed: 25976273
doi: 10.1002/jcb.25225
Salomon, J., Matusiak, L., Nowicka-Suszko, D. & Szepietowski, J. C. Chitinase-3-Like Protein 1 (YKL-40) Reflects the Severity of Symptoms in Atopic Dermatitis. J. Immunol. Res. 2017, 5746031 (2017).
pubmed: 28660216
pmcid: 5474268
doi: 10.1155/2017/5746031
Sohn, M. H. et al. Genetic variation in the promoter region of chitinase 3-like 1 is associated with atopy. Am. J .Respir. Crit. Care Med. 179, 449–456 (2009).
pubmed: 19106306
doi: 10.1164/rccm.200809-1422OC
Lee, Y. S. et al. New therapeutic strategy for atopic dermatitis by targeting CHI3L1/ITGA5 axis. Clin. Transl. Med. 12, e739 (2022).
pubmed: 35184414
pmcid: 8858621
doi: 10.1002/ctm2.739
Jeon, S. H. et al. Inhibition of Chitinase-3-like-1 by K284-6111 Reduces Atopic Skin Inflammation via Repressing Lactoferrin. Immune Netw. 21, e22 (2021).
pubmed: 34277112
pmcid: 8263211
doi: 10.4110/in.2021.21.e22