Myofibroblastic Differentiation of Human Skeletal Muscle‐Derived Progenitors Is Inhibited by Pirfenidone

Abstract

We identified a population within the human skeletal muscle (CD90+) capable of differentiating into myofibroblasts, the most important cells involved in fibrosis development, after stimulation with transforming growth factorbeta (TGFβ). Our objective was to characterize these progenitors and to evaluate the potential of Pirfenidone, a drug currently used for the treatment of idiopathic pulmonary fibrosis, to inhibit their myofibroblastic differentiation. Myofibroblastic differentiation was assessed with or without Pirfenidone treatment by measuring the expression of α‐smooth muscle actin (αSMA) and collagen type I at gene and protein levels as well as contractility. Pirfenidone inhibited the myofibroblastic differentiation as shown by a decrease of αSMA and collagen expression, lowered contractility and an inhibition of pro‐fibrotic genes. Suppression of Smad‐2 and ‐3 phosphorylation was shown to be involved as a mechanism through which Pirfenidone hindered the formation of myofibroblasts. Identifying myofibroblast progenitors in human skeletal muscle and showing the anti‐fibrotic effects of Pirfenidone is a step forward to better understand and treat muscle fibrosis observed in several muscle regenerative disorders.