Physiological and pathophysiological functions of NLRP6: pro- and anti-inflammatory roles.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
01 06 2022
01 06 2022
Historique:
received:
20
01
2022
accepted:
12
05
2022
entrez:
1
6
2022
pubmed:
2
6
2022
medline:
7
6
2022
Statut:
epublish
Résumé
The nucleotide-binding oligomerization and leucine-rich repeat receptor (NLR) protein family consists of important immune sensors that form inflammasomes, a cytosolic multi-protein platform that induces caspase-1 activation and is involved in different inflammatory pathologies. The NLR family pyrin domain containing 6 (NLRP6) is a receptor that can signal by forming inflammasomes, but which can also play an important role without forming inflammasomes. NLRP6 regulates intestinal homeostasis and inflammation, but also is involved in cancer, the nervous system or liver diseases, with both protective and deleterious consequences. In the present article, we review the different roles of NLRP6 in these processes and offer new insights into NLRP6 activation.
Identifiants
pubmed: 35650327
doi: 10.1038/s42003-022-03491-w
pii: 10.1038/s42003-022-03491-w
pmc: PMC9160023
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Carrier Proteins
0
Inflammasomes
0
Intracellular Signaling Peptides and Proteins
0
NLRP6 protein, human
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
524Informations de copyright
© 2022. The Author(s).
Références
Martinon, F., Burns, K. & Tschopp, J. The Inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell 10, 417–426 (2002).
pubmed: 12191486
doi: 10.1016/S1097-2765(02)00599-3
Ising, C. et al. NLRP3 inflammasome activation drives tau pathology. Nature 575, 669–673 (2019).
pubmed: 31748742
pmcid: 7324015
doi: 10.1038/s41586-019-1769-z
Jiang, D., Chen, S., Sun, R., Zhang, X. & Wang, D. The NLRP3 inflammasome: role in metabolic disorders and regulation by metabolic pathways. Cancer Lett. 419, 8–19 (2018).
pubmed: 29339210
doi: 10.1016/j.canlet.2018.01.034
Shen, H. H. et al. NLRP3: a promising therapeutic target for autoimmune diseases. Autoimmun. Rev. 17, 694–702 (2018).
pubmed: 29729449
doi: 10.1016/j.autrev.2018.01.020
Booshehri, L. M. & Hoffman, H. M. CAPS and NLRP3. J. Clin. Immunol. 39, 277–286 (2019).
pubmed: 31077002
pmcid: 8575304
doi: 10.1007/s10875-019-00638-z
Moghaddas, F. et al. Autoinflammatory mutation in NLRC4 reveals a leucine-rich repeat (LRR)–LRR oligomerization interface. J. Allergy Clin. Immunol. 142, 1956–1967.e6 (2018).
pubmed: 29778503
pmcid: 6281029
doi: 10.1016/j.jaci.2018.04.033
Hara, H. et al. The NLRP6 inflammasome recognizes lipoteichoic acid and regulates gram-positive pathogen infection. Cell 175, 1651–1664.e14 (2018).
pubmed: 30392956
pmcid: 6294477
doi: 10.1016/j.cell.2018.09.047
Vanaja, S. K., Rathinam, V. A. K. & Fitzgerald, K. A. Mechanisms of inflammasome activation: recent advances and novel insights. Trends Cell Biol. 25, 308–315 (2015).
pubmed: 25639489
pmcid: 4409512
doi: 10.1016/j.tcb.2014.12.009
Rathinam, V. A. K., Vanaja, S. K. & Fitzgerald, K. A. Regulation of inflammasome signaling. Nat. Immunol. 13, 333–342 (2012).
pubmed: 22430786
pmcid: 3523703
doi: 10.1038/ni.2237
Zoete, M. R. De, Palm, N. W., Zhu, S. & Flavell, R. A. Inflammasomes. Cold Spring Harb. Perspect. Biol. 6, a016287 (2014).
pubmed: 25324215
pmcid: 4292152
doi: 10.1101/cshperspect.a016287
Guo, H., Callaway, J. B. & Ting, J. P.-Y. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat. Med. 21, 677–687 (2015).
pubmed: 26121197
pmcid: 4519035
doi: 10.1038/nm.3893
Liston, A. & Masters, S. L. Homeostasis-altering molecular processes as mechanisms of inflammasome activation. Nat. Rev. Immunol. 17, 208–214 (2017).
pubmed: 28163301
doi: 10.1038/nri.2016.151
Broz, P. & Dixit, V. M. Inflammasomes: mechanism of assembly, regulation and signalling. Nat. Rev. Immunol. 16, 407–420 (2016).
pubmed: 27291964
doi: 10.1038/nri.2016.58
Kayagaki, N. et al. NINJ1 mediates plasma membrane rupture during lytic cell death. Nature 591, 131–136 (2021).
pubmed: 33472215
doi: 10.1038/s41586-021-03218-7
Franchi, L., Warner, N., Viani, K. & Nuñez, G. Function of Nod-like receptors in microbial recognition and host defense. Immunological Rev. 227, 106–128 (2010).
doi: 10.1111/j.1600-065X.2008.00734.x
Ghimire, L., Paudel, S., Jin, L. & Jeyaseelan, S. The NLRP6 inflammasome in health and disease. Mucosal Immunol. 13, 388–398 (2020).
pubmed: 31988468
pmcid: 7493825
doi: 10.1038/s41385-020-0256-z
Grenier, J. M. et al. Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-κB and caspase-1. FEBS Lett. 530, 73–78 (2002).
pubmed: 12387869
doi: 10.1016/S0014-5793(02)03416-6
Lin, Y. & Luo, Z. NLRP6 facilitates the interaction between TAB2/3 and TRIM38 in rheumatoid arthritis fibroblast-like synoviocytes. FEBS Lett. 591, 1141–1149 (2017).
pubmed: 28295271
doi: 10.1002/1873-3468.12622
Wlodarska, M. et al. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion. Cell 156, 1045–1059 (2014).
pubmed: 24581500
pmcid: 4017640
doi: 10.1016/j.cell.2014.01.026
Elinav, E. et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145, 745–757 (2011).
pubmed: 21565393
pmcid: 3140910
doi: 10.1016/j.cell.2011.04.022
Ydens, E. et al. Nlrp6 promotes recovery after peripheral nerve injury independently of inflammasomes. J. Neuroinflammation 12, 1–14 (2015).
doi: 10.1186/s12974-015-0367-8
Anand, P. K. et al. NLRP6 negatively regulates innate immunity and host defence against bacterial pathogens. Nature 488, 389–393 (2012).
pubmed: 22763455
pmcid: 3422416
doi: 10.1038/nature11250
Chen, G. Y., Liu, M., Wang, F., Bertin, J. & Núñez, G. A functional role for Nlrp6 in intestinal inflammation and tumorigenesis. J. Immunol. 186, 7187–7194 (2011).
pubmed: 21543645
doi: 10.4049/jimmunol.1100412
Bracey, N. A. et al. Tissue-selective alternate promoters guide NLRP6 expression. Life Sci. Alliance 4, 1–16 (2020).
Radulovic, K. et al. NLRP6 deficiency in CD4 T cells decreases T cell survival associated with increased cell death. J. Immunol. 203, 544–556 (2019).
pubmed: 31152078
doi: 10.4049/jimmunol.1800938
Valiño-Rivas, L. et al. Loss of NLRP6 expression increases the severity of acute kidney injury. Nephrol. Dial. Transplant. 35, 587–598 (2020).
pubmed: 31504777
doi: 10.1093/ndt/gfz169
Kempster, S. L. et al. Decelopmental control of the Nlrp6 inflammasome and a substrate,IL-18, in mammalian intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 300, 253–263 (2011).
doi: 10.1152/ajpgi.00397.2010
Wang, P. et al. Nlrp6 regulates intestinal antiviral innate immunity. Science 350, 826–830 (2015).
pubmed: 26494172
pmcid: 4927078
doi: 10.1126/science.aab3145
Nie, H. et al. MiR-331-3p inhibits inflammatory response after intracerebral hemorrhage by directly targeting NLRP6. BioMed. Res. Int. 2020, 6182464 (2020).
Xu, X. et al. microRNA-650 promotes inflammation induced apoptosis of intestinal epithelioid cells by targeting NLRP6. Biochem. Biophys. Res. Commun. 517, 551–556 (2019).
pubmed: 31399193
doi: 10.1016/j.bbrc.2019.06.077
Shen, C. et al. Molecular mechanism for NLRP6 inflammasome assembly and activation. Proc. Natl Acad. Sci. USA 116, 2052–2057 (2019).
pubmed: 30674671
pmcid: 6369754
doi: 10.1073/pnas.1817221116
Sharif, H. et al. Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome. Nature 570, 338–343 (2019).
pubmed: 31189953
pmcid: 6774351
doi: 10.1038/s41586-019-1295-z
Tapia-Abellán, A. et al. MCC950 closes the active conformation of NLRP3 to an inactive state. Nat. Chem. Biol. 15, 560–564 (2019).
pubmed: 31086329
pmcid: 7116292
doi: 10.1038/s41589-019-0278-6
Diebolder, C. A., Halff, E. F., Koster, A. J., Huizinga, E. G. & Koning, R. I. Cryoelectron tomography of the NAIP5/NLRC4 inflammasome: implications for NLR activation. Structure 23, 2349–2357 (2015).
pubmed: 26585513
doi: 10.1016/j.str.2015.10.001
Leng, F. et al. NLRP6 self-assembles into a linear molecular platform following LPS binding and ATP stimulation. Sci. Rep. 10, 1–10 (2020).
doi: 10.1038/s41598-019-57043-0
Kayagaki, N. et al. Non-canonical inflammasome activation targets caspase-11. Nature 479, 117–121 (2011).
pubmed: 22002608
doi: 10.1038/nature10558
Kayagaki, N. et al. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signaling. Nature 526, 666–671 (2015).
pubmed: 26375259
doi: 10.1038/nature15541
Alberti, S., Gladfelter, A. & Mittag, T. Considerations and challenges in studying liquid-liquid phase separation and biomolecular condensates. Cell 176, 419–434 (2019).
pubmed: 30682370
pmcid: 6445271
doi: 10.1016/j.cell.2018.12.035
Zbinden, A., Pérez-Berlanga, M., De Rossi, P. & Polymenidou, M. Phase separation and neurodegenerative diseases: a disturbance in the force. Dev. Cell 55, 45–68 (2020).
pubmed: 33049211
doi: 10.1016/j.devcel.2020.09.014
Zhu, G. et al. Phase separation of disease-associated SHP2 mutants underlies MAPK hyperactivation. Cell 183, 490–502.e18 (2020).
pubmed: 33002410
pmcid: 7572904
doi: 10.1016/j.cell.2020.09.002
Perdikari, T. M. et al. SARS-CoV-2 nucleocapsid protein phase-separates with RNA and with human hnRNPs. EMBO J. 39, e106478 (2020).
pubmed: 33200826
pmcid: 7737613
doi: 10.15252/embj.2020106478
Du, M. & Chen, Z. J. DNA-induced liquid phase condensation of cGAS activates innate immune signaling. Science 361, 704–709 (2018).
pubmed: 29976794
doi: 10.1126/science.aat1022
Shen, C. et al. Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome. Cell 184, 5759–5774 (2021).
pubmed: 34678144
doi: 10.1016/j.cell.2021.09.032
Tapia-Abellán, A. et al. Sensing low intracellular potassium by NLRP3 results in a stable open structure that promotes inflammasome activation. Sci. Adv. 7, eabf4468 (2021).
pubmed: 34524838
pmcid: 8443177
doi: 10.1126/sciadv.abf4468
Seregin, S. S. et al. NLRP6 protects Il10−/− mice from colitis by limiting colonization of Akkermansia muciniphila. Cell Rep. 19, 733–745 (2017).
pubmed: 28445725
pmcid: 5528001
doi: 10.1016/j.celrep.2017.03.080
Levy, M. et al. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163, 1428–1443 (2015).
pubmed: 26638072
pmcid: 5665753
doi: 10.1016/j.cell.2015.10.048
Hu, B. et al. Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proc. Natl Acad. Sci. USA 110, 9862–9867 (2013).
pubmed: 23696660
pmcid: 3683709
doi: 10.1073/pnas.1307575110
Radulovic, K. et al. A dietary flavone confers communicable protection against colitis through NLRP6 signaling independently of inflammasome activation. Mucosal Immunol. 11, 811–819 (2018).
pubmed: 29139477
doi: 10.1038/mi.2017.87
Sateriale, A. et al. The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6. Proc. Natl. Acad. Sci. USA 118, e2007807118 (2021).
Mao, X. et al. Candida albicans SC5314 inhibits NLRP3/NLRP6 inflammasome expression and dampens human intestinal barrier activity in Caco-2 cell monolayer model. Cytokine 126, 154882 (2020).
pubmed: 31629100
doi: 10.1016/j.cyto.2019.154882
Seregin, S. S. et al. NLRP6 function in inflammatory monocytes reduces susceptibility to chemically induced intestinal injury. Mucosal Immunol. 10, 434–445 (2017).
pubmed: 27353251
doi: 10.1038/mi.2016.55
Hansson, G. C. & Johansson, M. E. V. The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteria. Gut Microbes 1, 51–54 (2010).
pubmed: 21327117
pmcid: 3035142
doi: 10.4161/gmic.1.1.10470
Okumura, R. et al. Lypd8 promotes the segregation of flagellated microbiota and colonic epithelia. Nature 532, 117–121 (2016).
pubmed: 27027293
doi: 10.1038/nature17406
Vaishnava, S. et al. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334, 255–258 (2011).
pubmed: 21998396
pmcid: 3321924
doi: 10.1126/science.1209791
Birchenough, G. M. H., Nystrom, E. E. L., Johansson, M. E. V. & Hansson, G. C. A sentinel goblet cell guards the colonic crypt by triggering Nlrp6-dependent Muc2 secretion. Science 352, 1535–1542 (2016).
pubmed: 27339979
pmcid: 5148821
doi: 10.1126/science.aaf7419
Volk, J. K. et al. The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function. J. Exp. Med. 216, 2602–2618 (2019).
pubmed: 31420376
pmcid: 6829596
doi: 10.1084/jem.20190679
Xing, J. et al. DHX15 is required to control RNA virus-induced intestinal inflammation. Cell Rep. 35, 109205 (2021).
pubmed: 34161762
pmcid: 8276442
doi: 10.1016/j.celrep.2021.109205
dos Santos Ramos, A., Viana, G. C. S., de Macedo Brigido, M. & Almeida, J. F. Neutrophil extracellular traps in inflammatory bowel diseases: Implications in pathogenesis and therapeutic targets. Pharmacol. Res. 171, 105779 (2021).
pubmed: 34298111
doi: 10.1016/j.phrs.2021.105779
Sollberger, G. et al. Gasdermin D plays a vital role in the generation of neutrophil extracellular traps. Sci. Immunol. 3, eaar6689 (2018).
pubmed: 30143555
doi: 10.1126/sciimmunol.aar6689
Ranson, N. et al. Nod-like receptor pyrin-containing protein 6 (NLRP6) is up-regulated in ileal Crohn’s disease and differentially expressed in goblet cells. Cell Mol. Gastroenterol. Hepatol. 6, 110–112.e8 (2018).
pubmed: 29928676
pmcid: 6007817
doi: 10.1016/j.jcmgh.2018.03.001
Alipour, M. et al. Mucosal barrier depletion and loss of bacterial diversity are primary abnormalities in paediatric ulcerative colitis. J. Crohns Colitis 10, 462–471 (2016).
pubmed: 26660940
doi: 10.1093/ecco-jcc/jjv223
Mukherjee, S. et al. Deubiquitination of NLRP6 inflammasome by Cyld critically regulates intestinal inflammation. Nat. Immunol. 21, 626–635 (2020).
pubmed: 32424362
pmcid: 7881443
doi: 10.1038/s41590-020-0681-x
Leach, S. T. et al. Local and systemic interleukin-18 and interleukin-18-binding protein in children with inflammatory bowel disease. Inflamm. Bowel Dis. 14, 68–74 (2008).
pubmed: 17879274
doi: 10.1002/ibd.20272
León, A. J. et al. High levels of proinflammatory cytokines, but not markers of tissue injury, in unaffected intestinal areas from patients with IBD. Mediators Inflamm. 2009, 580450 (2009).
pubmed: 19657406
pmcid: 2719754
doi: 10.1155/2009/580450
Toubai, T. et al. Disease independent of gut microbial composition. Nat. Microbiol. 4, 800–812 (2020).
doi: 10.1038/s41564-019-0373-1
Wang, X. et al. NLRP6 suppresses gastric cancer growth via GRP78 ubiquitination. Exp. Cell Res. 395, 112177 (2020).
pubmed: 32682010
doi: 10.1016/j.yexcr.2020.112177
Piunti, A. & Shilatifard, A. The roles of Polycomb repressive complexes in mammalian development and cancer. Nat. Rev. Mol. Cell Biol. 22, 326–345 (2021).
pubmed: 33723438
doi: 10.1038/s41580-021-00341-1
Bai, Y. Long noncoding RNA OIP5 ‐ AS1 aggravates cell proliferation, migration in gastric cancer by epigenetically silencing NLRP6 expression via binding EZH2. J. Cell Biochem. 121, 353–362 (2019).
pubmed: 31219209
doi: 10.1002/jcb.29183
Lotfollahzadeh, S., Taherian, M. & Anand, S. Hirschsprung Disease (StatPearls Publishing, 2021).
Tomuschat, C., Virbel, C. R., O’Donnell, A. M. & Puri, P. Reduced expression of the NLRP6 inflammasome in the colon of patients with Hirschsprung’s disease. J. Pediatr. Surg. 54, 1573–1577 (2019).
pubmed: 30262203
doi: 10.1016/j.jpedsurg.2018.08.059
Ghimire, L. et al. NLRP6 negatively regulates pulmonary host defense in Gram-positive bacterial infection through modulating neutrophil recruitment and function. PLoS Pathog. 14, 1–24 (2018).
doi: 10.1371/journal.ppat.1007308
Rigby, K. M. & DeLeo, F. R. Neutrophils in innate host defense against Staphylococcus aureus infections. Semin. Immunopathol. 34, 237–259 (2012).
pubmed: 22080185
doi: 10.1007/s00281-011-0295-3
Cai, S. et al. NLRP6 modulates neutrophil homeostasis in bacterial pneumonia-derived sepsis. Mucosal Immunol. 14, 574–584 (2021).
pubmed: 33230225
doi: 10.1038/s41385-020-00357-4
Xu, D. et al. The critical role of nlrp6 inflammasome in streptococcus pneumoniae infection in vitro and in vivo. Int. J. Mol. Sci. 22, 3876 (2021).
pubmed: 33918100
pmcid: 8069100
doi: 10.3390/ijms22083876
Liu, W., Liu, J., Wang, W., Wang, Y. & Ouyang, X. NLRP6 induces pyroptosis by activation of caspase-1 in gingival fibroblasts. J. Dent. Res. 97, 1391–1398 (2018).
pubmed: 29791256
doi: 10.1177/0022034518775036
Johnson, D. E. et al. Head and neck squamous cell carcinoma. Nat. Rev. Dis. Prim. 6, 1–92 (2020).
Shen, Y. et al. Novel prognostic model established for patients with head and neck squamous cell carcinoma based on pyroptosis-related genes. Transl. Oncol. 14, 101233 (2021).
pubmed: 34600420
pmcid: 8487076
doi: 10.1016/j.tranon.2021.101233
Yu, Y., Cao, F., Xiong, Y. & Zhou, H. SP1 transcriptionally activates NLRP6 inflammasome and induces immune evasion and radioresistance in glioma cells. Int. Immunopharmacol. 98, 107858 (2021).
pubmed: 34147913
doi: 10.1016/j.intimp.2021.107858
Jia, G. et al. Screening of gene markers related to the prognosis of metastatic skin cutaneous melanoma based on Logit regression and survival analysis. BMC Med. Genomics 14, 1–11 (2021).
doi: 10.1186/s12920-021-00923-0
Zhu, Y. et al. Effects of NLRP6 on the proliferation and activation of human hepatic stellate cells. Exp. Cell Res. 370, 383–388 (2018).
pubmed: 29966662
doi: 10.1016/j.yexcr.2018.06.040
Arthur, M. J. Fibrogenesis II. Metalloproteinases and their inhibitors in liver fibrosis. Am. J. Physiol. Gastrointest. Liver Physiol. 279, G245–G249 (2000).
pubmed: 10915630
doi: 10.1152/ajpgi.2000.279.2.G245
Huang, C. et al. Hepatocyte-specific deletion of Nlrp6 in mice exacerbates the development of non-alcoholic steatohepatitis. Free Radic. Biol. Med. 169, 110–121 (2021).
pubmed: 33857628
doi: 10.1016/j.freeradbiomed.2021.04.008
Ji, X. et al. NLRP6 exerts a protective role via NF-kB with involvement of CCL20 in a mouse model of alcoholic hepatitis. Biochem. Biophys. Res. Commun. 528, 485–492 (2020).
pubmed: 32507279
doi: 10.1016/j.bbrc.2020.05.171
Schneider, K. M. et al. Intestinal dysbiosis amplifies acetaminophen-induced acute liver injury. Cell Mol. Gastroenterol. Hepatol. 11, 909–933 (2021).
pubmed: 33189892
doi: 10.1016/j.jcmgh.2020.11.002
Li, M. et al. NLRP6 deficiency aggravates liver injury after allogeneic hematopoietic stem cell transplantation. Int. Immunopharmacol. 74, 105740 (2019).
pubmed: 31301646
doi: 10.1016/j.intimp.2019.105740
Almadi, M. A. et al. New insights into gastrointestinal and hepatic granulomatous disorders. Nat. Rev. Gastroenterol. Hepatol. 8, 455–466 (2011).
pubmed: 21818145
doi: 10.1038/nrgastro.2011.115
Sanches, R. C. O. et al. NLRP6 plays an important role in early hepatic immunopathology caused by Schistosoma mansoni infection. Front. Immunol. 11, 1–12 (2020).
doi: 10.3389/fimmu.2020.00795
Chensue, S. W. Chemokines in innate and adaptive granuloma formation. Front. Immunol. 4, 43 (2013).
pubmed: 23444049
pmcid: 3580335
doi: 10.3389/fimmu.2013.00043
Muller, P. A. et al. Microbiota-modulated CART(+) enteric neurons autonomously regulate blood glucose. Science 370, 314–321 (2020).
pubmed: 32855216
pmcid: 7886298
doi: 10.1126/science.abd6176
Matheis, F. et al. Adrenergic signaling in muscularis macrophages limits infection-induced neuronal loss. Cell 180, 64–78.e16 (2020).
pubmed: 31923400
pmcid: 7271821
doi: 10.1016/j.cell.2019.12.002
Wang, P. F. et al. NLRP6 inflammasome ameliorates brain injury after intracerebral hemorrhage. Front. Cell. Neurosci. 11, 1–9 (2017).
pubmed: 28154525
pmcid: 5243839
doi: 10.3389/fncel.2017.00206
Huang, X. et al. BRCC3 promotes activation of the NLRP6 inflammasome following cerebral ischemia/reperfusion (I/R) injury in rats. Neurosci. Lett. 756, 135954 (2021).
pubmed: 33979701
doi: 10.1016/j.neulet.2021.135954
Zheng, C. M. et al. Nicotine causes nephrotoxicity through the induction of nlrp6 inflammasome and alpha7 nicotinic acetylcholine receptor. Toxics 8, 1–16 (2020).
doi: 10.3390/toxics8040092
Pickup, L., Radhakrishnan, A., Townend, J. N. & Ferro, C. J. Arterial stiffness in chronic kidney disease: a modifiable cardiovascular risk factor? Curr. Opin. Nephrol. Hypertens. 28, 527–536 (2019).
pubmed: 31361609
doi: 10.1097/MNH.0000000000000535
Glorioso, N. et al. Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population. PLoS ONE 8, 6–11 (2013).
doi: 10.1371/journal.pone.0077562
Albrecht, M., Domingues, F. S., Schreiber, S. & Lengauer, T. Identification of mammalian orthologs associates PYPAF5 with distinct functional roles. FEBS Lett. 538, 173–177 (2003).
pubmed: 12633874
doi: 10.1016/S0014-5793(03)00161-3
Gieger, C. et al. New gene functions in megakaryopoiesis and platelet formation. Nature 480, 201–208 (2011).
pubmed: 22139419
pmcid: 3335296
doi: 10.1038/nature10659