Human Keratoconus Cell Contractility is Mediated by Transforming Growth Factor-Beta Isoforms
AbstractKeratoconus (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
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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.
Lyon D, McKay TB, Sarkar-Nag A, Priyadarsini S, Karamichos D. Human Keratoconus Cell Contractility is Mediated by Transforming Growth Factor-Beta Isoforms. Journal of Functional Biomaterials. 2015; 6(2):422-438.Chicago/Turabian Style
Lyon, Desiree'; McKay, Tina B.; Sarkar-Nag, Akhee; Priyadarsini, Shrestha; Karamichos, Dimitrios. 2015. "Human Keratoconus Cell Contractility is Mediated by Transforming Growth Factor-Beta Isoforms." J. Funct. Biomater. 6, no. 2: 422-438.