{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:06:10Z","timestamp":1788404770664,"version":"build-2803163510"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T00:00:00Z","timestamp":1680739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Sicca Forschungsf\u00f6rderung 2021 of the Professional Association of German Ophthalmologists (BVA)","award":["PA738\/15-1"],"award-info":[{"award-number":["PA738\/15-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["PA738\/15-1"],"award-info":[{"award-number":["PA738\/15-1"]}]},{"name":"Ernst-Muck Foundation FAU Erlangen-N\u00fcrnberg","award":["PA738\/15-1"],"award-info":[{"award-number":["PA738\/15-1"]}]},{"name":"Natural Sciences and Engineering Council of Canada (NSERC)","award":["PA738\/15-1"],"award-info":[{"award-number":["PA738\/15-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inadequate wound healing of ocular surface injuries can lead to permanent visual impairment. The relaxin ligand-receptor system has been demonstrated to promote corneal wound healing through increased cell migration and modulation of extracellular matrix formation. Recently, C1q\/tumor necrosis factor-related protein (CTRP) 8 was identified as a novel interaction partner of relaxin receptor RXFP1. Additional data also suggest a role for CTRP1 and CTRP6 in RXFP1-mediated cAMP signaling. However, the role of CTRP1, CTRP6 and CTRP8 at the ocular surface remains unclear. In this study, we investigated the effects of CTRP1, CTRP6, and CTRP8 on epithelial ocular surface wound closure and their dependence on the RXFP1 receptor pathway. CTRP1, CTRP6, and CTRP8 expression was analyzed by RT-PCR and immunohistochemistry in human tissues and cell lines derived from the ocular surface and lacrimal apparatus. In vitro ocular surface wound modeling was performed using scratch assays. We analyzed the effects of recombinant CTRP1, CTRP6, and CTRP8 on cell proliferation and migration in human corneal and conjunctival epithelial cell lines. Dependence on RXFP1 signaling was established by inhibiting ligand binding to RXFP1 using a specific anti-RXFP1 antibody. We detected the expression of CTRP1, CTRP6, and CTRP8 in human tissue samples of the cornea, conjunctiva, meibomian gland, efferent tear ducts, and lacrimal gland, as well as in human corneal, conjunctival, and meibomian gland epithelial cell lines. Scratch assays revealed a dose-dependent increase in the closure rate of surface defects in human corneal epithelial cells after treatment with CTRP1, CTRP6, and CTRP8, but not in conjunctival epithelial cells. Inhibition of RXFP1 fully attenuated the effect of CTRP8 on the closure rate of surface defects in human corneal epithelial cells, whereas the CTRP1 and CTRP6 effects were not completely suppressed. Conclusions: Our findings demonstrate a novel role for CTRP1, CTRP6, and CTRP8 in corneal epithelial wound closure and suggest an involvement of the relaxin receptor RXFP1 signaling pathway. This could be a first step toward new approaches for pharmacological and therapeutic intervention.<\/jats:p>","DOI":"10.3390\/ijms24076839","type":"journal-article","created":{"date-parts":[[2023,4,6]],"date-time":"2023-04-06T05:54:39Z","timestamp":1680760479000},"page":"6839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["C1q\/TNF-Related Proteins 1, 6 and 8 Are Involved in Corneal Epithelial Wound Closure by Targeting Relaxin Receptor RXFP1 In Vitro"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8363-8269","authenticated-orcid":false,"given":"Hagen Fabian","family":"Nicolaus","sequence":"first","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"},{"name":"Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0448-6741","authenticated-orcid":false,"given":"Thomas","family":"Klonisch","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, College of Medicine, Winnipeg, MB R3E 0J9, Canada"},{"name":"Department of Pathology, Rady Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB R3E 3P5, Canada"},{"name":"Department of Medical Microbiology & Infectious Diseases, Rady Faculty of Health Sciences, College of Medicine, University of Manitoba, Winnipeg, MB R3E 0J9, Canada"},{"name":"Research Institute in Oncology and Hematology (RIOH), Cancer Care Manitoba, Winnipeg, MB R3E 0J9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0527-0953","authenticated-orcid":false,"given":"Friedrich","family":"Paulsen","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Garreis","sequence":"additional","affiliation":[{"name":"Institute of Functional and Clinical Anatomy, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.preteyeres.2015.07.002","article-title":"Progress in corneal wound healing","volume":"49","author":"Ljubimov","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s00347-021-01423-3","article-title":"Corneal wound healing-Pathophysiology and principles","volume":"118","author":"Brockmann","year":"2021","journal-title":"Ophthalmologe"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7780","DOI":"10.1167\/iovs.12-10714","article-title":"Relaxin 2 is functional at the ocular surface and promotes corneal wound healing","volume":"53","author":"Hampel","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.1210\/en.2012-2201","article-title":"Insulin-like factor 3 promotes wound healing at the ocular surface","volume":"154","author":"Hampel","year":"2013","journal-title":"Endocrinology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1002\/path.4257","article-title":"C1q-tumour necrosis factor-related protein 8 (CTRP8) is a novel interaction partner of relaxin receptor RXFP1 in human brain cancer cells","volume":"231","author":"Glogowska","year":"2013","journal-title":"J. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1042\/BJ20081240","article-title":"Molecular, biochemical and functional characterizations of C1q\/TNF family members: Adipose-tissue-selective expression patterns, regulation by PPAR-gamma agonist, cysteine-mediated oligomerizations, combinatorial associations and metabolic functions","volume":"416","author":"Wong","year":"2008","journal-title":"Biochem. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"127","DOI":"10.3389\/fendo.2015.00127","article-title":"RXFP1 is Targeted by Complement C1q Tumor Necrosis Factor-Related Factor 8 in Brain Cancer","volume":"6","author":"Thanasupawat","year":"2015","journal-title":"Front. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.tem.2011.12.003","article-title":"CTRP family: Linking immunity to metabolism","volume":"23","author":"Buechler","year":"2012","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.bbrc.2009.08.014","article-title":"CTRP8 and CTRP9B are novel proteins that hetero-oligomerize with C1q\/TNF family members","volume":"388","author":"Peterson","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1111\/bph.13559","article-title":"Structural commonality of C1q TNF-related proteins and their potential to activate relaxin\/insulin-like family peptide receptor 1 signalling pathways in cancer cells","volume":"174","author":"Klonisch","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E678","DOI":"10.1152\/ajpendo.00087.2016","article-title":"Loss of CTRP1 disrupts glucose and lipid homeostasis","volume":"311","author":"Rodriguez","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.freeradbiomed.2018.05.004","article-title":"C1QTNF1 attenuates angiotensin II-induced cardiac hypertrophy via activation of the AMPKa pathway","volume":"121","author":"Wu","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1096\/fj.15-279885","article-title":"C1q\/TNF-related protein-1 functions to protect against acute ischemic injury in the heart","volume":"30","author":"Yuasa","year":"2016","journal-title":"FASEB J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.atherosclerosis.2016.04.024","article-title":"C1q\/TNF-related protein 1 links macrophage lipid metabolism to inflammation and atherosclerosis","volume":"250","author":"Wang","year":"2016","journal-title":"Atherosclerosis"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s13258-018-0770-5","article-title":"C1q and TNF related protein 1 regulates expression of inflammatory genes in vascular smooth muscle cells","volume":"41","author":"Kim","year":"2019","journal-title":"Genes Genom."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1097\/MAJ.0000000000000378","article-title":"Plasma levels of C1q\/TNF-related protein 1 and interleukin 6 in patients with acute coronary syndrome or stable angina pectoris","volume":"349","author":"Tang","year":"2015","journal-title":"Am. J. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/pr.2018.16","article-title":"Serum levels of C1q\/tumor necrosis factor-related protein-1 in children with Kawasaki disease","volume":"83","author":"Feng","year":"2018","journal-title":"Pediatr. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3953","DOI":"10.1016\/j.febslet.2006.06.034","article-title":"Tumor necrosis factor-alpha and interleukin-1beta increases CTRP1 expression in adipose tissue","volume":"580","author":"Kim","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.mce.2013.01.002","article-title":"A novel adipokine C1q\/TNF-related protein 1 (CTRP1) regulates chondrocyte proliferation and maturation through the ERK1\/2 signaling pathway","volume":"369","author":"Akiyama","year":"2013","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Park, R., Jang, M., Park, Y.I., Park, Y., Namkoong, S., Lee, J.I., and Park, J. (2021). Elevated Levels of CTRP1 in Obesity Contribute to Tumor Progression in a p53-Dependent Manner. Cancers, 13.","DOI":"10.3390\/cancers13143619"},{"key":"ref_21","first-page":"2582416","article-title":"Identification of CTRP1 as a Prognostic Biomarker and Oncogene in Human Glioblastoma","volume":"2019","author":"Chen","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1007\/s00592-018-1203-2","article-title":"C1q\/TNF-related protein-6 is associated with insulin resistance and the development of diabetes in Chinese population","volume":"55","author":"Wang","year":"2018","journal-title":"Acta Diabetol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.clnesp.2021.11.013","article-title":"Effect of Paleolithic-based low-carbohydrate vs. moderate-carbohydrate diets with portion-control and calorie-counting on CTRP6, asprosin and metabolic markers in adults with metabolic syndrome: A randomized clinical trial","volume":"48","author":"Shemirani","year":"2022","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8483","DOI":"10.1038\/ncomms9483","article-title":"CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis","volume":"6","author":"Murayama","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s10059-010-0088-x","article-title":"C1qTNF-related protein-6 increases the expression of interleukin-10 in macrophages","volume":"30","author":"Kim","year":"2010","journal-title":"Mol. Cells"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"173755","DOI":"10.1016\/j.ejphar.2020.173755","article-title":"Role of the CTRP6\/AMPK pathway in kidney fibrosis through the promotion of fatty acid oxidation","volume":"892","author":"Xie","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s00395-015-0492-7","article-title":"C1q\/tumor necrosis factor-related protein-6 attenuates post-infarct cardiac fibrosis by targeting RhoA\/MRTF-A pathway and inhibiting myofibroblast differentiation","volume":"110","author":"Lei","year":"2015","journal-title":"Basic Res. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.biopha.2017.10.091","article-title":"CTRP6 inhibits cell proliferation and ECM expression in rat mesangial cells cultured under TGF-\u03b21","volume":"97","author":"Wang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.bbrc.2016.05.013","article-title":"CTRP6 inhibits fibrogenesis in TGF-\u03b21-stimulated human dermal fibroblasts","volume":"475","author":"Fan","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17059","DOI":"10.1002\/jcb.28967","article-title":"Inhibition of CTRP6 prevented survival and migration in hepatocellular carcinoma through inactivating the AKT signaling pathway","volume":"120","author":"Wan","year":"2019","journal-title":"J. Cell Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1186\/s12935-021-02377-x","article-title":"C1QTNF6 promotes oral squamous cell carcinoma by enhancing proliferation and inhibiting apoptosis","volume":"21","author":"Song","year":"2021","journal-title":"Cancer Cell Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4967","DOI":"10.1007\/s11033-019-04947-9","article-title":"An adiponectin paralog protein, CTRP6 decreased the proliferation and invasion activity of oral squamous cell carcinoma cells: Possible interaction with laminin receptor pathway","volume":"46","author":"Hano","year":"2019","journal-title":"Mol. Biol. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1002\/1878-0261.12981","article-title":"Novel CTRP8-RXFP1-JAK3-STAT3 axis promotes Cdc42-dependent actin remodeling for enhanced filopodia formation and motility in human glioblastoma cells","volume":"16","author":"Glogowska","year":"2022","journal-title":"Mol. Oncol."},{"key":"ref_34","first-page":"614","article-title":"An SV40-immortalized human corneal epithelial cell line and its characterization","volume":"36","author":"Ohashi","year":"1995","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2496","DOI":"10.1167\/iovs.02-0851","article-title":"Mucin gene expression in immortalized human corneal-limbal and conjunctival epithelial cell lines","volume":"44","author":"Gipson","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1167\/iovs.04-0528","article-title":"Characterization of growth and differentiation in a telomerase-immortalized human corneal epithelial cell line","volume":"46","author":"Robertson","year":"2005","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4263","DOI":"10.1167\/iovs.03-0560","article-title":"Characterization of a spontaneously immortalized cell line (IOBA-NHC) from normal human conjunctiva","volume":"44","author":"Diebold","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jtos.2018.04.005","article-title":"Effect of intermittent shear stress on corneal epithelial cells using an in vitro flow culture model","volume":"16","author":"Hampel","year":"2018","journal-title":"Ocul. Surf."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1007\/s00418-010-0713-y","article-title":"Roles of human beta-defensins in innate immune defense at the ocular surface: Arming and alarming corneal and conjunctival epithelial cells","volume":"134","author":"Garreis","year":"2010","journal-title":"Histochem. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.exer.2017.03.011","article-title":"The human meibomian gland epithelial cell line as a model to study meibomian gland dysfunction","volume":"163","author":"Hampel","year":"2017","journal-title":"Exp. Eye Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5968","DOI":"10.1167\/iovs.17-22637","article-title":"Expression and Regulation of S100 Fused-Type Protein Hornerin at the Ocular Surface and Lacrimal Apparatus","volume":"58","author":"Garreis","year":"2017","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"474","DOI":"10.2164\/jandrol.110.012625","article-title":"Effect of relaxin on human sperm functions","volume":"33","author":"Ferlin","year":"2012","journal-title":"J. Androl."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5785","DOI":"10.1002\/jcp.30262","article-title":"C1q\/tumor necrosis factor-related protein-6 attenuates TNF-\u03b1-induced apoptosis in salivary acinar cells via AMPK\/SIRT1-modulated miR-34a-5p expression","volume":"236","author":"Qu","year":"2021","journal-title":"J. Cell Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1055\/a-0929-6072","article-title":"Circulating CTRP6 Levels are Increased in Overweight or Obese Chinese Individuals and Associated with Insulin Resistance Parameters: A Pilot Study","volume":"129","author":"Liao","year":"2021","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosis.2019.04.222","article-title":"The novel adipokine CTRP1 is significantly associated with the incidence of major adverse cardiovascular events","volume":"286","author":"Muendlein","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13098-021-00631-w","article-title":"The circulating levels of CTRP1 and CTRP5 are associated with obesity indices and carotid intima-media thickness (cIMT) value in patients with type 2 diabetes: A preliminary study","volume":"13","author":"Majidi","year":"2021","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Yagmur, E., Buergerhausen, D., Koek, G.H., Weiskirchen, R., Trautwein, C., Koch, A., and Tacke, F. (2019). Elevated CTRP1 Plasma Concentration Is Associated with Sepsis and Pre-Existing Type 2 Diabetes Mellitus in Critically Ill Patients. J. Clin. Med., 8.","DOI":"10.3390\/jcm8050661"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"5479627","DOI":"10.1155\/2016\/5479627","article-title":"Circulating CTRP1 Levels in Type 2 Diabetes and Their Association with FGF21","volume":"2016","author":"Han","year":"2016","journal-title":"Int. J. Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1507\/endocrj.EJ14-0016","article-title":"Elevated circulating levels of CTRP1, a novel adipokine, in diabetic patients","volume":"61","author":"Xin","year":"2014","journal-title":"Endocr. J."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Shabani, P., Naeimi Khaledi, H., Beigy, M., Emamgholipour, S., Parvaz, E., Poustchi, H., and Doosti, M. (2015). Circulating level of CTRP1 in patients with nonalcoholic fatty liver disease (NAFLD): Is it through insulin resistance?. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118650"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Pan, X., Lu, T., Wu, F., Jin, L., Zhang, Y., Shi, L., Li, X., and Lin, Z. (2014). Circulating complement-C1q TNF-related protein 1 levels are increased in patients with type 2 diabetes and are associated with insulin sensitivity in Chinese subjects. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094478"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4183781","DOI":"10.1155\/2019\/4183781","article-title":"Circulating CTRP1 Levels Are Increased and Associated with the STOD in Essential Hypertension in Chinese Patients","volume":"2019","author":"Su","year":"2019","journal-title":"Cardiovasc. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Wang, H., Wang, R., Du, D., Li, F., and Li, Y. (2016). Serum levels of C1q\/TNF-related protein-1 (CTRP-1) are closely associated with coronary artery disease. BMC Cardiovasc. Disord., 16.","DOI":"10.1186\/s12872-016-0266-7"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1177\/0300060519847372","article-title":"Association of C1q\/TNF-related protein-1 (CTRP1) serum levels with coronary artery disease","volume":"47","author":"Shen","year":"2019","journal-title":"J. Int. Med. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2009.07.031","article-title":"Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome","volume":"314","author":"Maury","year":"2010","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"S64","DOI":"10.1210\/jc.2008-1613","article-title":"Adipocytokines and the metabolic complications of obesity","volume":"93","author":"Rasouli","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMra043430","article-title":"Inflammation, atherosclerosis, and coronary artery disease","volume":"352","author":"Hansson","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"117992","DOI":"10.1016\/j.lfs.2020.117992","article-title":"C1q\/tumor necrosis factor-related protein-1 attenuates microglia autophagy and inflammatory response by regulating the Akt\/mTOR pathway","volume":"256","author":"Wang","year":"2020","journal-title":"Life Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1097\/ICO.0b013e3181a16578","article-title":"Analysis of inflammatory cytokines in the tears of dry eye patients","volume":"28","author":"Massingale","year":"2009","journal-title":"Cornea"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"108089","DOI":"10.1016\/j.exer.2020.108089","article-title":"Corneal wound healing","volume":"197","author":"Wilson","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1006\/exer.1994.1081","article-title":"Epidermal growth factor, transforming growth factor alpha, transforming growth factor beta, acidic fibroblast growth factor, basic fibroblast growth factor, and interleukin-1 proteins in the cornea","volume":"59","author":"Wilson","year":"1994","journal-title":"Exp. Eye Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1097\/00003226-199707000-00015","article-title":"IL-1 upregulates keratinocyte growth factor and hepatocyte growth factor mRNA and protein production by cultured stromal fibroblast cells: Interleukin-1 beta expression in the cornea","volume":"16","author":"Weng","year":"1997","journal-title":"Cornea"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Park, R., Park, Y.I., Park, Y., Lee, S., So, J., and Park, J. (2022). CTRP1 Knockout Attenuates Tumor Progression in A549 and HCT116 Cancer Cells. Cancers, 14.","DOI":"10.3390\/cancers14184495"},{"key":"ref_64","first-page":"2400","article-title":"IL-6 induction in desiccated corneal epithelium in vitro and in vivo","volume":"17","author":"Higuchi","year":"2011","journal-title":"Mol. Vis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1128\/IAI.67.5.2497-2502.1999","article-title":"Expression of interleukin-6 in the cornea in response to infection with different strains of Pseudomonas aeruginosa","volume":"67","author":"Cole","year":"1999","journal-title":"Infect. Immun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1076\/ceyr.23.6.406.6969","article-title":"The role of IL-1beta in the regulation of IL-8 and IL-6 in human corneal epithelial cells during Pseudomonas aeruginosa colonization","volume":"23","author":"Xue","year":"2001","journal-title":"Curr. Eye Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.exer.2014.06.012","article-title":"IL-6 as a corneal wound healing mediator in an in vitro scratch assay","volume":"125","author":"Diebold","year":"2014","journal-title":"Exp. Eye Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8549","DOI":"10.1167\/iovs.11-7956","article-title":"Role of the IL-6 classic- and trans-signaling pathways in corneal sterile inflammation and wound healing","volume":"52","author":"Ebihara","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1097\/00003226-199907000-00011","article-title":"Differential effects of epidermal growth factor and interleukin 6 on corneal epithelial cells and vascular endothelial cells","volume":"18","author":"Nakamura","year":"1999","journal-title":"Cornea"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s00347-003-0950-8","article-title":"Corneal wound healing. II. Treatment of disorders of wound healing","volume":"100","author":"Rieck","year":"2003","journal-title":"Ophthalmologe"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1124\/jpet.110.170977","article-title":"Prevention of bleomycin-induced pulmonary fibrosis by a novel antifibrotic peptide with relaxin-like activity","volume":"335","author":"Pini","year":"2010","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s11596-020-2145-9","article-title":"CTRP1 Attenuates UUO-induced Renal Fibrosis via AMPK\/NOX4 Pathway in Mice","volume":"40","author":"Li","year":"2020","journal-title":"Curr. Med. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1681\/ASN.2019060597","article-title":"AT1R-AT2R-RXFP1 Functional Crosstalk in Myofibroblasts: Impact on the Therapeutic Targeting of Renal and Cardiac Fibrosis","volume":"30","author":"Chow","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"10681","DOI":"10.1016\/S0021-9258(18)87000-4","article-title":"Relaxin modulates synthesis and secretion of procollagenase and collagen by human dermal fibroblasts","volume":"265","author":"Unemori","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/j.1523-1755.2005.00384.x","article-title":"The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway","volume":"68","author":"Heeg","year":"2005","journal-title":"Kidney Int."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1016\/j.bbrc.2017.09.110","article-title":"Relaxin alleviates TGF\u03b21-induced cardiac fibrosis via inhibition of Stat3-dependent autophagy","volume":"493","author":"Yuan","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6839\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:11:08Z","timestamp":1760123468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,6]]},"references-count":76,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076839"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076839","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,6]]}}}