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J. Funct. Biomater. 2015, 6(2), 422-438; doi:10.3390/jfb6020422

Human Keratoconus Cell Contractility is Mediated by Transforming Growth Factor-Beta Isoforms

1
Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
2
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Francesco Puoci
Received: 12 May 2015 / Revised: 29 May 2015 / Accepted: 10 June 2015 / Published: 18 June 2015
(This article belongs to the Special Issue Ocular Tissue Engineering)
View Full-Text   |   Download PDF [2842 KB, uploaded 18 June 2015]   |  

Abstract

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-β (TGF-β). We have previously identified alterations in the TGF-β 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-β isoforms. HKCs showed delayed contractility with decreased Collagen I:Collagen V ratios. TGF-β1 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. View Full-Text
Keywords: keratoconus; transforming growth factor-β; collagen gels; extracellular matrix; matrix metalloproteases keratoconus; transforming growth factor-β; collagen gels; extracellular matrix; matrix metalloproteases
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Lyon, D.; McKay, T.B.; Sarkar-Nag, A.; Priyadarsini, S.; Karamichos, D. Human Keratoconus Cell Contractility is Mediated by Transforming Growth Factor-Beta Isoforms. J. Funct. Biomater. 2015, 6, 422-438.

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J. Funct. Biomater. EISSN 2079-4983 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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