Calponin 1 contributes to myofibroblast differentiation of human pleural mesothelial cells.
Young-Yeon ChooTsuyoshi SakaiSatoshi KomatsuReiko IkebeAnn JeffersKaran P SinghSteven IdellTorry A TuckerMitsuo IkebePublished in: American journal of physiology. Lung cellular and molecular physiology (2022)
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-β (TGF-β) induced marked upregulation of calponin 1 expression, which was correlated with notable cytoskeletal rearrangement in human PMCs (HPMCs) to produce stress fibers. Downregulation of calponin 1 expression reduced stress fiber formation. Interestingly, induced stress fibers predominantly contain α-smooth muscle actin (αSMA) associated with calponin 1 but not β-actin. Calponin 1-associated stress fibers also contained myosin II and α-actinin. Furthermore, focal adhesions were aligned with the produced stress fibers. These results suggest that calponin 1 facilitates formation of stress fibers that resemble contractile myofibrils. Supporting this notion, TGF-β 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 stiffness of scar tissue in pleura to promote pleural fibrosis (PF) and that upregulation of calponin 1 plays a central role in this process.
Keyphrases
- transforming growth factor
- smooth muscle
- poor prognosis
- high glucose
- induced apoptosis
- endothelial cells
- epithelial mesenchymal transition
- signaling pathway
- cell cycle arrest
- skeletal muscle
- cell proliferation
- stress induced
- stem cells
- binding protein
- bone marrow
- endoplasmic reticulum stress
- diabetic rats
- oxidative stress
- heat stress
- pi k akt
- high resolution