The role of Ski protein in the modulation of cardiac myofibroblast phenotype: MMP expression and function
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Date
2015
Authors
Kavosh, Morvarid Sadat
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Abstract
Cardiac fibrosis results from excessive formation of the extracellular matrix by activated cardiac myofibroblasts. Ski, an endogenous repressor of the profibrotic factor transforming growth factor-β1, has been shown to attenuate the myofibroblast phenotype. We demonstrate that Ski regulates rat cardiac myofibroblast’s capacity for ECM remodeling, further solidifying its putative role as an endogenous anti-fibrotic TGF-β1 repressor. We show that Ski overexpression alters matrix metalloproteinase-2 and 9 expression and activity via immunoblotting and zymography. We also observe an attenuation of paxillin, a focal adhesion associated protein, and FAK (Tyr 397) expression by immunoblotting. Additionally, myofibroblast motility is reduced by Ski overexpression via transwell migration and scratch assay. We suggest that Ski may exert multiple effects on adverse ECM remodeling by altering the expression and function of the ECM proteases. The effects of Ski on cell motility also represent a putative mechanism for modulation of myofibroblast function in progression of cardiac fibrosis.
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Ski