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Ascorbic acid promotes a TGFβ1‐induced myofibroblast phenotype switch

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l‐Ascorbic acid (AA), generally known as vitamin C, is a crucial cofactor for a variety of enzymes, including prolyl‐3‐hydroxylase (P3H), prolyl‐4‐hydroxylase (P4H), and lysyl hydroxylase (LH)‐mediated collagen maturation. Here, we… Click to show full abstract

l‐Ascorbic acid (AA), generally known as vitamin C, is a crucial cofactor for a variety of enzymes, including prolyl‐3‐hydroxylase (P3H), prolyl‐4‐hydroxylase (P4H), and lysyl hydroxylase (LH)‐mediated collagen maturation. Here, we investigated whether AA has additional functions in the regulation of the myofibroblast phenotype, besides its function in collagen biosynthesis. We found that AA positively influences TGFβ1‐induced expression of COL1A1, ACTA2, and COL4A1. Moreover, we demonstrated that AA promotes αSMA stress fiber formation as well as the synthesis and deposition of collagens type I and IV. Additionally, AA amplified the contractile phenotype of the myofibroblasts, as seen by increased contraction of a 3D collagen lattice. Moreover, AA increased the expression of several TGFβ1‐induced genes, including DDR1 and CCN2. Finally, we demonstrated that the mechanism of AA action seems independent of Smad2/3 signaling.

Keywords: phenotype; ascorbic acid; myofibroblast phenotype; tgf induced; acid promotes

Journal Title: Physiological Reports
Year Published: 2017

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