期刊
JOURNAL OF FUNCTIONAL BIOMATERIALS
卷 6, 期 2, 页码 422-438出版社
MDPI
DOI: 10.3390/jfb6020422
关键词
keratoconus; transforming growth factor-beta; collagen gels; extracellular matrix; matrix metalloproteases
资金
- National Institutes of Health Grants/National Eye Institute [5R01EY023568, 5R01EY020886]
- Research to Prevent Blindness (New York, NY, USA)
- NEI/DMEI Cellular Imaging Core Facility at OUHSC [P30EY021725]
- National Eye Institute of the NIH [T32EY023202]
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-beta (TGF-beta). We have previously identified alterations in the TGF-beta 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-beta isoforms. HKCs showed delayed contractility with decreased Collagen I:Collagen V ratios. TGF-beta 1 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.
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