TGF-β1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

摘要: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates mesenchymal cells which underlie sites unresolved epithelial injury and associated progression fibrosis. However, the cellular origins these phenotypes remain unclear. We examined whether potent fibrogenic cytokine TGF-β1 could induce transition (EMT) human alveolar cell line, A549, investigated signaling pathway TGF-β1-mediated EMT. A549 were for evidence EMT after treatment TGF-β1. was assessed by: morphology under phase-contrast microscopy; Western analysis lysates expression phenotypic markers including fibronectin EDA (Fn-EDA), E-cadherin (E-cad). Markers fibrogenesis, collagens connective tissue growth factor (CTGF) also evaluated by measuring mRNA level using RT-PCR, protein immunofluorescence or blotting. Signaling pathways characterized monoclonal antibodies to detect phosphorylated Erk1/2 Smad2 presence absence MEK inhibitors. The role siRNA. data showed that TGF-β1, but not TNF-α IL-1β, induced an type II phenotype undergo a time-and concentration-dependent manner. process accompanied morphological alteration fibroblast Fn-EDA vimentin, concomitant downregulation marker E-cad. Furthermore, had undergone enhanced fibrogenesis I III CTGF. MMP-2 evidenced. TGF-β1-induced occurred through phosphorylation inhibited gene silencing; inhibitors failed attenuate either EMT-associated observed changes. Our study shows induces via activation. support concept cells, suggest need further studies investigate phenomenon.