{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T23:52:38Z","timestamp":1789689158180,"version":"4.0.1"},"reference-count":71,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T00:00:00Z","timestamp":1434585600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000053","name":"NEI","doi-asserted-by":"publisher","award":["5R01EY023568"],"award-info":[{"award-number":["5R01EY023568"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NEI","doi-asserted-by":"publisher","award":["5R01EY020886"],"award-info":[{"award-number":["5R01EY020886"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NEI","doi-asserted-by":"publisher","award":["T32EY023202"],"award-info":[{"award-number":["T32EY023202"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"NEI","doi-asserted-by":"publisher","award":["P30EY021725"],"award-info":[{"award-number":["P30EY021725"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JFB"],"abstract":"<jats:p>Keratoconus (KC) is a progressive disease linked to defects in the structural components of the corneal stroma. The extracellular matrix (ECM) is secreted and assembled by corneal keratocytes and regulated by transforming growth factor-\u03b2 (TGF-\u03b2). We have previously identified alterations in the TGF-\u03b2 pathway in human keratoconus cells (HKCs) compared to normal corneal fibroblasts (HCFs). In our current study, we seeded HKCs and HCFs in 3D-collagen gels to identify variations in contractility, and expression of matrix metalloproteases (MMPs) by HKCs in response the TGF-\u03b2 isoforms. HKCs showed delayed contractility with decreased Collagen I:Collagen V ratios. TGF-\u03b21 significantly increased ECM contraction, Collagen I, and Collagen V expression by HKCs. We also found that HKCs have significantly decreased Collagen I:Collagen III ratios suggesting a potential link to altered collagen isoform expression in KC. Our findings show that HKCs have significant variations in collagen secretion in a 3D collagen gel and have delayed contraction of the matrix compared to HCFs. For the first time, we utilize a collagen gel model to characterize the contractility and MMP expression by HKCs that may contribute to the pathobiology of KC.<\/jats:p>","DOI":"10.3390\/jfb6020422","type":"journal-article","created":{"date-parts":[[2015,6,18]],"date-time":"2015-06-18T10:08:54Z","timestamp":1434622134000},"page":"422-438","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Human Keratoconus Cell Contractility is Mediated by Transforming Growth Factor-Beta Isoforms"],"prefix":"10.3390","volume":"6","author":[{"given":"Desiree'","family":"Lyon","sequence":"first","affiliation":[{"name":"Department of Ophthalmology\/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"McKay","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City,  OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhee","family":"Sarkar-Nag","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology\/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrestha","family":"Priyadarsini","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology\/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8761-3824","authenticated-orcid":false,"given":"Dimitrios","family":"Karamichos","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology\/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA"},{"name":"Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City,  OK 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.jmbbm.2010.09.014","article-title":"The effect of keratoconus on the structural, mechanical, and optical properties of the cornea","volume":"4","author":"Ambekar","year":"2011","journal-title":"J. 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