Uncovering the role of transient receptor potential channels in pterygium: a machine learning approach.

Humans Pterygium / genetics Transient Receptor Potential Channels / genetics Reproducibility of Results Conjunctiva MicroRNAs / genetics
Gene signature Immune landscape Machine learning Pterygium Therapy Transient receptor potential channels

Journal

Inflammation research : official journal of the European Histamine Research Society ... [et al.]
ISSN: 1420-908X
Titre abrégé: Inflamm Res
Pays: Switzerland
ID NLM: 9508160

Informations de publication

Date de publication:
Mar 2023
Historique:
received: 19 09 2022
accepted: 11 01 2023
revised: 04 01 2023
pubmed: 25 1 2023
medline: 22 3 2023
entrez: 24 1 2023
Statut: ppublish

Résumé

We aimed at identifying the role of transient receptor potential (TRP) channels in pterygium. Based on microarray data GSE83627 and GSE2513, differentially expressed genes (DEGs) were screened and 20 hub genes were selected. After gene correlation analysis, 5 TRP-related genes were obtained and functional analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed. Multifactor regulatory network including mRNA, microRNAs (miRNAs) and transcription factors (TFs) was constructed. The 5 gene TRP signature for pterygium was validated by multiple machine learning (ML) programs including support vector classifiers (SVC), random forest (RF), and k-nearest neighbors (KNN). Additionally, we outlined the immune microenvironment and analyzed the candidate drugs. Finally, in vitro experiments were performed using human conjunctival epithelial cells (CjECs) to confirm the bioinformatics results. Five TRP-related genes (MCOLN1, MCOLN3, TRPM3, TRPM6, and TRPM8) were validated by ML algorithms. Functional analyses revealed the participation of lysosome and TRP-regulated inflammatory pathways. A comprehensive immune infiltration landscape and TFs-miRNAs-mRNAs network was studied, which indicated several therapeutic targets (LEF1 and hsa-miR-455-3p). Through correlation analysis, MCOLN3 was proposed as the most promising immune-related biomarker. In vitro experiments further verified the reliability of our in silico results and demonstrated that the 5 TRP-related genes could influence the proliferation and proinflammatory signaling in conjunctival tissue contributing to the pathogenesis of pterygium. Our study suggested that TRP channels played an essential role in the pathogenesis of pterygium. The identified pivotal biomarkers (especially MCOLN3) and pathways provide novel directions for future mechanistic and therapeutic studies for pterygium.

Identifiants

DOI: 10.1007/s00011-023-01693-4 PMID: 36692516
pubmed: 36692516
doi: 10.1007/s00011-023-01693-4
pii: 10.1007/s00011-023-01693-4
doi:

Substances chimiques

Transient Receptor Potential Channels 0
MicroRNAs 0
MCOLN3 protein, human 0
MIRN455 microRNA, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

589-602

Subventions

Organisme : National Natural Science Foundation of China
ID : 81770888

Informations de copyright

© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Références

Liu L, Wu J, Geng J, Yuan Z, Huang D. Geographical prevalence and risk factors for pterygium: a systematic review and meta-analysis. BMJ Open. 2013;3: e003787.
pubmed: 24253031 pmcid: 3840351 doi: 10.1136/bmjopen-2013-003787
Zhao Z, Zhang J, Liang H, et al. Corneal reinnervation and sensitivity recovery after pterygium excision. J Ophthalmol. 2020;2020:1–8.
Van Acker SI, Van den Bogerd B, Haagdorens M, et al. Pterygium—the good, the bad, and the ugly. Cells. 2021;10:1567.
pubmed: 34206333 pmcid: 8305200 doi: 10.3390/cells10071567
Chui J, Coroneo MT, Tat LT, et al. Ophthalmic pterygium. Am J Pathol. 2011;178:817–27.
pubmed: 21281814 pmcid: 3069871 doi: 10.1016/j.ajpath.2010.10.037
Artornsombudh P, Sanpavat A, Tinnungwattana U, et al. Prevalence and clinicopathologic findings of conjunctival epithelial neoplasia in pterygia. Ophthalmology. 2013;120:1337–40.
pubmed: 23499063 doi: 10.1016/j.ophtha.2012.12.020
Ghiasian L, Samavat B, Hadi Y, Arbab M, Abolfathzadeh N. Recurrent pterygium: a review. J Curr Ophthalmol. 2021;33:367.
pubmed: 35128181 doi: 10.4103/joco.joco_153_20
Chu WK, Choi HL, Bhat AK, Jhanji V. Pterygium: new insights. Eye. 2020;34:1047–50.
pubmed: 32029918 pmcid: 7413326 doi: 10.1038/s41433-020-0786-3
Bradley JC, Yang W, Bradley RH, Reid TW, Schwab IR. The science of pterygia. Br J Ophthalmol. 2010;94:815–20.
pubmed: 19515643 doi: 10.1136/bjo.2008.151852
Nilius B, Voets T, Peters J. TRP channels in disease. Sci STKE. 2005;2005(295):8.
doi: 10.1126/stke.2952005re8
Wang H, Cheng X, Tian J, et al. TRPC channels: structure, function, regulation and recent advances in small molecular probes. Pharmacol Ther. 2020;209: 107497.
pubmed: 32004513 pmcid: 7183440 doi: 10.1016/j.pharmthera.2020.107497
Julius D. TRP channels and pain. Annu Rev Cell Dev Biol. 2013;29:355–84.
pubmed: 24099085 doi: 10.1146/annurev-cellbio-101011-155833
Nilius B, Owsianik G. The transient receptor potential family of ion channels. Genome Biol. 2011;12:218.
pubmed: 21401968 pmcid: 3129667 doi: 10.1186/gb-2011-12-3-218
Khajavi N, Reinach PS, Slavi N, et al. Thyronamine induces TRPM8 channel activation in human conjunctival epithelial cells. Cell Signal. 2015;27:315–25.
pubmed: 25460045 doi: 10.1016/j.cellsig.2014.11.015
Pan Z, Wang Z, Yang H, Zhang F, Reinach PS. TRPV1 activation is required for hypertonicity-stimulated inflammatory cytokine release in human corneal epithelial cells. Investig Opthalmology Vis Sci. 2011;52:485.
doi: 10.1167/iovs.10-5801
Hirata H, Oshinsky ML. Ocular dryness excites two classes of corneal afferent neurons implicated in basal tearing in rats: involvement of transient receptor potential channels. J Neurophysiol. 2012;107:1199–209.
pubmed: 22114162 doi: 10.1152/jn.00657.2011
Trusiano B, Tupik JD, Allen IC. Cold sensor, hot topic: TRPM8 plays a role in monocyte function and differentiation. J Leukoc Biol. 2022;112:361.
pubmed: 35570407 doi: 10.1002/JLB.3CE0222-099R
Assimakopoulou M, Pagoulatos D, Nterma P, Pharmakakis N. Immunolocalization of cannabinoid receptor type 1 and CB2 cannabinoid receptors, and transient receptor potential vanilloid channels in pterygium. Mol Med Rep. 2017;16:5285–93.
pubmed: 28849159 pmcid: 5647061 doi: 10.3892/mmr.2017.7246
Goecks J, Jalili V, Heiser LM, Gray JW. How machine learning will transform biomedicine. Cell. 2020;181:92–101.
pubmed: 32243801 pmcid: 7141410 doi: 10.1016/j.cell.2020.03.022
Ye B, Liu K, Cao S, et al. Discrimination of indoor versus outdoor environmental state with machine learning algorithms in myopia observational studies. J Transl Med. 2019;17:314.
pubmed: 31533735 pmcid: 6751881 doi: 10.1186/s12967-019-2057-2
An G, Omodaka K, Tsuda S, et al. Comparison of machine-learning classification models for glaucoma management. J Healthc Eng. 2018;2018:1–8.
doi: 10.1155/2018/6874765
Yan H, Shan X, Wei S, Liu F, Li W, Lei Y, et al. Abnormal spontaneous brain activities of limbic-cortical circuits in patients with dry eye disease. Front Hum Neurosci. 2020;14: 574758.
pubmed: 33304254 pmcid: 7693447 doi: 10.3389/fnhum.2020.574758
Nwanosike EM, Conway BR, Merchant HA, Hasan SS. Potential applications and performance of machine learning techniques and algorithms in clinical practice: a systematic review. Int J Med Inf. 2022;159: 104679.
doi: 10.1016/j.ijmedinf.2021.104679
Banna HU, Zanabli A, McMillan B, et al. Evaluation of machine learning algorithms for trabeculectomy outcome prediction in patients with glaucoma. Sci Rep. 2022;12:2473.
pubmed: 35169235 pmcid: 8847459 doi: 10.1038/s41598-022-06438-7
Sugimoto K, Murata H, Hirasawa H, et al. Cross-sectional study: does combining optical coherence tomography measurements using the ‘Random Forest’ decision tree classifier improve the prediction of the presence of perimetric deterioration in glaucoma suspects? BMJ Open. 2013;3: e003114.
pubmed: 24103806 pmcid: 3796272 doi: 10.1136/bmjopen-2013-003114
Muhammad H, Fuchs TJ, De Cuir N, et al. Hybrid deep learning on single wide-field optical coherence tomography scans accurately classifies glaucoma suspects. J Glaucoma. 2017;26:1086–94.
pubmed: 29045329 pmcid: 5716847 doi: 10.1097/IJG.0000000000000765
Joshi VS, Maude RJ, Reinhardt JM, et al. Automated detection of malarial retinopathy-associated retinal hemorrhages. Investig Opthalmol Vis Sci. 2012;53:6582.
doi: 10.1167/iovs.12-10191
Kishore B, Ananthamoorthy NP. Glaucoma classification based on intra-class and extra-class discriminative correlation and consensus ensemble classifier. Genomics. 2020;112:3089–96.
pubmed: 32470644 doi: 10.1016/j.ygeno.2020.05.017
Zheng J. Molecular mechanism of TRP channels. Compr Physiol. 2013;3(1):221–42.
pubmed: 23720286 pmcid: 3775668 doi: 10.1002/cphy.c120001
Venkatachalam K, Montell C. TRP Channels. Annu Rev Biochem. 2007;76:387–417.
pubmed: 17579562 pmcid: 4196875 doi: 10.1146/annurev.biochem.75.103004.142819
Wu N, Yan C, Chen J, et al. Conjunctival reconstruction via enrichment of human conjunctival epithelial stem cells by p75 through the NGF-p75-SALL2 signaling axis. Stem Cells Transl Med. 2020;9:1448.
pubmed: 32602639 pmcid: 7581450 doi: 10.1002/sctm.19-0449
Wu N, Gong D, Chen J, et al. Design of functional decellularized matrix for conjunctival epithelial stem cell maintenance and ocular surface reconstruction. Mater Des. 2022;224: 111278.
doi: 10.1016/j.matdes.2022.111278
Arora S, Rana R, Chhabra A, Jaiswal A, Rani V. miRNA–transcription factor interactions: a combinatorial regulation of gene expression. Mol Genet Genom. 2013;288:77–87.
doi: 10.1007/s00438-013-0734-z
Golu T, Mogoant L, Streba CT, Pirici DN. Pterygium: histological and immunohistochemical aspects. Rom J Morphol Embryol. 2011;52(1):153–8.
pubmed: 21424047
Tekelioglu Y, Turk A, Avunduk AM, Yulug E. Flow cytometrical analysis of adhesion molecules, T-lymphocyte subpopulations and inflammatory markers in pterygium. Ophthalmologica. 2006;220:372–8.
pubmed: 17095882 doi: 10.1159/000095863
Di Girolamo N, Chui J, Coroneo MT, Wakefield D. Pathogenesis of pterygia: role of cytokines, growth factors, and matrix metalloproteinases. Prog Retin Eye Res. 2004;23:195–228.
pubmed: 15094131 doi: 10.1016/j.preteyeres.2004.02.002
Bianchp E, Grande C, Platerotp R, et al. Immunohistochemical profile of VEGF, TGF-β and PGE
doi: 10.1177/039463201202500307
Kim SW, Kim H-I, Thapa B, Nuwormegbe S, Lee K. Critical role of mTORC2-Akt signaling in TGF-β1-induced myofibroblast differentiation of human pterygium fibroblasts. Investig Opthalmol Vis Sci. 2019;60:82.
doi: 10.1167/iovs.18-25376
Xie J, Ning Q, Zhang H, Ni S, Ye J. RhoA/ROCK signaling regulates TGF-β1-Induced fibrotic effects in human pterygium fibroblasts through MRTF-A. Curr Eye Res. 2022;47:196–205.
pubmed: 34323621 doi: 10.1080/02713683.2021.1962363
Vrenken KS, Jalink K, van Leeuwen FN, Middelbeek J. Beyond ion-conduction: channel-dependent and -independent roles of TRP channels during development and tissue homeostasis. Biochim Biophys Acta BBA Mol Cell Res. 2016;1863:1436–46.
doi: 10.1016/j.bbamcr.2015.11.008
Gan N, Han Y, Zeng W, Wang Y, Xue J, Jiang Y. Structural mechanism of allosteric activation of TRPML1 by PI(3,5)P
pubmed: 35131932 pmcid: 8851561 doi: 10.1073/pnas.2120404119
Jaslan D, Böck J, Krogsaeter E, Grimm C. Evolutionary aspects of TRPMLs and TPCs. Int J Mol Sci. 2020;21:4181.
pubmed: 32545371 pmcid: 7312350 doi: 10.3390/ijms21114181
Li G, Huang D, Li N, Ritter JK, Li P-L. Regulation of TRPML1 channel activity and inflammatory exosome release by endogenously produced reactive oxygen species in mouse podocytes. Redox Biol. 2021;43:102013.
pubmed: 34030116 pmcid: 8163985 doi: 10.1016/j.redox.2021.102013
Wakabayashi K, Gustafson AM, Sidransky E, Goldin E. Mucolipidosis type IV: an update. Mol Genet Metab. 2011;104:206–13.
pubmed: 21763169 pmcid: 3205274 doi: 10.1016/j.ymgme.2011.06.006
Noben-Trauth K. The TRPML3 channel: from gene to function. Adv Exp Med Biol. 2011;704:229–37.
pubmed: 21290299 doi: 10.1007/978-94-007-0265-3_13
Miao Y, Li G, Zhang X, Xu H, Abraham SN. A TRP channel senses lysosome neutralization by pathogens to trigger their expulsion. Cell. 2015;161:1306–19.
pubmed: 26027738 pmcid: 4458218 doi: 10.1016/j.cell.2015.05.009
Kim HJ, Soyombo AA, Tjon-Kon-Sang S, So I, Muallem S. The Ca2+ channel TRPML3 regulates membrane trafficking and autophagy. Traffic Cph Den. 2009;10:1157–67.
doi: 10.1111/j.1600-0854.2009.00924.x
Zierler S. TRPM channels as potential therapeutic targets against pro-inflammatory diseases. Cell Calcium. 2017;67:105.
pubmed: 28549569 doi: 10.1016/j.ceca.2017.05.002
Held K, Voets T, Vriens J. TRPM3 in temperature sensing and beyond. Temp Austin Tex. 2015;2:201–13.
Takashina Y, Manabe A, Hasegawa H, et al. Sodium citrate increases expression and flux of Mg2+ transport carriers mediated by activation of MEK/ERK/c-Fos pathway in renal tubular epithelial cells. Nutrients. 2018;10:E1345.
doi: 10.3390/nu10101345
Yang F, Cai J, Zhan H, et al. Suppression of TRPM7 inhibited hypoxia-induced migration and invasion of androgen-independent prostate cancer cells by enhancing RACK1-Mediated degradation of HIF-1α. Oxid Med Cell Longev. 2020;2020:6724810.
pubmed: 32215176 pmcid: 7079255
Khalil M, Babes A, Lakra R, et al. Transient receptor potential melastatin 8 ion channel in macrophages modulates colitis through a balance-shift in TNF-alpha and interleukin-10 production. Mucosal Immunol. 2016;9:1500–13.
pubmed: 26982596 doi: 10.1038/mi.2016.16
Chui J, Girolamo ND, Wakefield D, Coroneo MT. The pathogenesis of pterygium: current concepts and their therapeutic implications. Ocul Surf. 2008;6:24–43.
pubmed: 18264653 doi: 10.1016/S1542-0124(12)70103-9
Anguria P, Carmichael T, Ntuli S, Kitinya J. Chronic inflammatory cells and damaged limbal cells in pterygium. Afr Health Sci. 2013;13:725–30.
pubmed: 24250313 pmcid: 3824424
Garreis F, Schroder A, Reinach PS, et al. Upregulation of transient receptor potential vanilloid Type-1 channel activity and and Ca2+ influx dysfunction in human pterygial cells. Invest Ophthalmol Vis Sci. 2016;57(6):2564–77.
pubmed: 27163769 doi: 10.1167/iovs.16-19170
Sumioka T, Okada Y, Reinach PS, et al. Impairment of corneal epithelial wound healing in a TRPV1-deficient mouse. Investig Opthalmol Vis Sci. 2014;55:3295.
doi: 10.1167/iovs.13-13077
Hobert O. Common logic of transcription factor and microRNA action. Trends Biochem Sci. 2004;29:462–8.
pubmed: 15337119 doi: 10.1016/j.tibs.2004.07.001
Ghafouri-Fard S, Abak A, Fattahi F, et al. The interaction between miRNAs/lncRNAs and nuclear factor-κB (NF-κB) in human disorders. Biomed Pharmacother Biomed Pharmacother. 2021;138: 111519.
pubmed: 33756159 doi: 10.1016/j.biopha.2021.111519
Ueta M, Nishigaki H, Sotozono C, et al. Regulation of gene expression by miRNA-455-3p, upregulated in the conjunctival epithelium of patients with Stevens-Johnson syndrome in the chronic stage. Sci Rep. 2020;10:17239.
pubmed: 33057072 pmcid: 7560850 doi: 10.1038/s41598-020-74211-9
Kato N, Shimmura S, Kawakita T, et al. β-Catenin activation and epithelial-mesenchymal transition in the pathogenesis of pterygium. Investig Opthalmol Vis Sci. 2007;48:1511.
doi: 10.1167/iovs.06-1060
Huebner K, Procházka J, Monteiro AC, Mahadevan V, Schneider-Stock R. The activating transcription factor 2: an influencer of cancer progression. Mutagenesis. 2019;34:375–89.
pubmed: 31799611 pmcid: 6923166 doi: 10.1093/mutage/gez041
Katoh M. Genomic testing, tumor microenvironment and targeted therapy of Hedgehog-related human cancers. Clin Sci. 2019;133:953–70.
doi: 10.1042/CS20180845
Principe DR. Patients deriving long-term benefit from immune checkpoint inhibitors demonstrate conserved patterns of site-specific mutations. Sci Rep. 2022;12:11490.
pubmed: 35798829 pmcid: 9263148 doi: 10.1038/s41598-022-15714-5
Tong L, Lan W, Lim RR, Chaurasia SS. S100A proteins as molecular targets in the ocular surface inflammatory diseases. Ocul Surf. 2014;12:23–31.
pubmed: 24439044 doi: 10.1016/j.jtos.2013.10.001
Maxia C, Murtas D, Corrias M, et al. Vitamin D and vitamin D receptor in patients with ophthalmic pterygium. Eur J Histochem. 2017;61(4):2837.
pubmed: 29313597 pmcid: 5686448 doi: 10.4081/ejh.2017.2837
Skurikhin E, Pershina O, Zhukova M, et al. Spiperone stimulates regeneration in pulmonary endothelium damaged by cigarette smoke and lipopolysaccharide. Int J Chron Obstruct Pulmon Dis. 2021;16:3575–91.
pubmed: 35002229 pmcid: 8722540 doi: 10.2147/COPD.S336410
Skurikhin E, Madonov P, Pershina O, et al. Micellar hyaluronidase and spiperone as a potential treatment for pulmonary fibrosis. Int J Mol Sci. 2021;22:5599.
pubmed: 34070506 pmcid: 8198946 doi: 10.3390/ijms22115599
Kistemaker LEM, Gosens R. Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling. Trends Pharmacol Sci. 2015;36:164–71.
pubmed: 25511176 doi: 10.1016/j.tips.2014.11.005
Yang Q, Jhanji V, Tan SQ, et al. Continuous exposure of nicotine and cotinine retards human primary pterygium cell proliferation and migration. J Cell Biochem. 2019;120:4203–13.
pubmed: 30260034 doi: 10.1002/jcb.27707

Auteurs

Yuchen Cai (Y)

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Huangpu District, Shanghai, 200011, China.
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.

Tianyi Zhou (T)

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Huangpu District, Shanghai, 200011, China.
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.

Jin Chen (J)

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Huangpu District, Shanghai, 200011, China.
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.

Xueyao Cai (X)

Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Huangpu District, Shanghai, 200011, China. billy112544op@gmail.com.

Yao Fu (Y)

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhi-Zao-Ju Road, Huangpu District, Shanghai, 200011, China. drfuyao@126.com.
Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China. drfuyao@126.com.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Uncovering the role of transient receptor...
questionsmedicales.fr › Maladies de l'oeil › Maladies de la conjonctive › Ptérygion › Uncovering the role of transient receptor...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Canaux cationiques TRP › Uncovering the role of transient receptor...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Reproductibilité des résultats › Uncovering the role of transient receptor...
questionsmedicales.fr › Organes des sens › Oeil › Paupières › Conjonctive › Uncovering the role of transient receptor...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › microARN › Uncovering the role of transient receptor...