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

Journal of Functional Biomaterials

Desiree’ Lyon¹  Tina B. McKay²  Akhee Sarkar-Nag¹  Shrestha Priyadarsini¹  Dimitrios Karamichos¹ 

[1] Department of Ophthalmology/Dean McGee Eye Institute, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; E-Mails:;Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; E-Mail:

关键词: keratoconus;    transforming growth factor-β;    collagen gels;    extracellular matrix;    matrix metalloproteases;   

DOI  :  10.3390/jfb6020422

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.