Calponin 1 contributes to myofibroblast differentiation of human pleural mesothelial cells

Pleural mesothelial cells (PMCs) can become myofibroblasts via mesothelial-mesenchymal transition (MesoMT) and contribute to pleural organization, fibrosis, and rind formation. However, how these transformed mesothelial cells contribute to lung fibrosis remains unclear. Here, we investigated the mechanism of contractile myofibroblast differentiation of PMCs. Transforming growth factor -beta (TGF-beta) induced marked upregulation of calponin 1 expression, which was correlated with notable cytoskeletal rear-rangement in human PMCs (HPMCs) to produce stress fibers. Downregulation of calponin 1 expression reduced stress fiber for-mation. Interestingly, induced stress fibers predominantly contain alpha-smooth muscle actin (alpha SMA) associated with calponin 1 but not beta-actin. Calponin 1-associated stress fibers also contained myosin II and alpha-actinin. Furthermore, focal adhesions were aligned with the produced stress fibers. These results suggest that calponin 1 facilitates formation of stress fibers that resemble contract-ile myofibrils. Supporting this notion, TGF-beta significantly increased the contractile activity of HPMCs, an effect that was abolished by downregulation of calponin 1 expression. We infer that differentiation of HPMCs to contractile myofibroblasts facilitates stiff-ness of scar tissue in pleura to promote pleural fibrosis (PF) and that upregulation of calponin 1 plays a central role in this process.