C2C12 myoblasts differentiate into myofibroblasts via the TGF-β1 signaling pathway mediated by Fibulin2

Abstract

Myoblasts play a critical role in the regeneration of skeletal muscle following injury. It has been reported that local elevation of transforming growth factor-β1 (TGF-β1) after skeletal muscle injury induces differentiation of myoblasts into myofibroblasts. However, the mechanisms underlying this differentiation process remain incompletely understood. In this study, we found that Fibulin2 expression significantly increases in myoblasts in response to TGF-β1 stimulation. Elevated Fibulin2 levels enhance the expression of fibrotic markers. Conversely, downregulation of Fibulin2 in myoblasts inhibits the upregulation of fibrotic markers induced by TGF-β1 stimulation. Extracellular secretion of Fibulin2 activates the TGF-β1-Smad2 pathway, thereby promoting the upregulation of fibrotic markers. Hence, Fibulin2 and TGF-β1 form a positive feedback loop that facilitates differentiation of myoblasts into myofibroblasts.