The role of α-smooth muscle actin in fibroblast-mediated matrix contraction and remodeling

Publication date: Available online 4 November 2016 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Author(s): Arti V. Shinde, Claudio Humeres, Nikolaos G. Frangogiannis Cardiac myofibroblasts play an important role in myocardial remodeling. Although α-smooth muscle actin (α-SMA) expression is the hallmark of mature myofibroblasts, its role in regulating fibroblast function remains poorly understood. We explore the effects of the matrix environment in modulating cardiac fibroblast phenotype, and we investigate the role of α-SMA in fibroblast function using loss- and gain-of-function approaches. In murine myocardial infarction, infiltration of the infarct border zone with abundant α-SMA-positive myofibroblasts was associated with scar contraction. Isolated cardiac fibroblasts cultured in plates showed high α-SMA expression localized in stress fibers, exhibited activation of focal adhesion kinase (FAK), and synthesized large amounts of extracellular matrix proteins. In contrast, when these cells were cultured in collagen lattices, they exhibited marked reduction of α-SMA expression, negligible FAK activation, attenuated collagen synthesis, and increased transcription of genes associated with matrix metabolism. Transforming Growth Factor-β1-mediated contraction of fibroblast-populated collagen pads was associated with accentuated α-SMA synthesis. In contrast, serum- and basic Fibroblast Growth Factor-induced collagen pad contraction was associ...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research