P120-catenin regulates pulmonary fibrosis and TGF-β induced lung fibroblast differentiation

In this study, we investigated the expression and role of P120 in pulmonary fibrosis and transforming growth factor beta (TGF-β) mediated lung fibroblast-to-myofibroblast differentiation (fibroblast differentiation). Our data indicated that P120 expression increased in lung fibrotic foci and primary lung fibroblasts isolated from bleomycin- (BLM) challenged mice, compared to controls. In vitro, TGF-β induced P120 expression in human lung fibroblasts, and siRNA-mediated SMAD3 depletion inhibited TGF-β stimulated P120 expression. Blocking nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway through chemical inhibitor or knockdown of NF-kB p65 subunit also suppressed TGF-β induced P120 expression in human lung fibroblast. Knockdown of P120 expression inhibited TGF-β induced human lung fibroblast differentiation, as well as suppressed the activation of SMAD and ERK signaling pathways. Administration of lentivirus coding mouse P120 sh-RNA into mouse lung tissue dramatically attenuated the expression of P120 in lung tissue and lung fibroblast, suppressed BLM induced increase of TGF-β, alpha smooth muscle actin (α-SMA) and fibronectin (FN) expression, and decreased the deposition of collagen and pulmonary fibrosis. Collectively, these results suggested that P120 involved in lung fibroblast differentiation and pulmonary fibrosis, and inhibition of P120 expression decreased pulmonary fibrosis in BLM challenged mice. Thus, attenuation of P120 expression...

Source: Life Sciences - May 22, 2019 Category: Biology Source Type: research