Abstract
Transforming growth factor-β (TGF-β) signaling and TGF-β-promoted epithelial-to-mesenchymal transition (EMT) have been postulated to be the common pathway causing pulmonary fibrosis. However, the up- or downstreaming markers of TGF-β-induced EMT still need to be further recognized. In the present study, we investigated the regulation on Krüppel-like factor 4 (KLF-4) and plasminogen activator inhibitor-1 (PAI-1) by TGF-β in the murine lung epithelial LA-4 cells and then examined the regulation of both markers in the TGF-β-induced EMT by the PAI-1 knockdown or the KLF-4 overexpression. Our study indicated that TGF-β induced EMT in mouse LA-4 lung epithelial cells via reducing E-cadherin, while promoting Collagen I and α-SMA. And PAI-1 was upregulated, whereas KLF-4 was downregulated in the TGF-β-induced EMT model in LA-4 cells. Moreover, the siRNA-mediated PAI-1 knockdown inhibited the TGF-β-induced EMT, whereas the adenovirus-medicated KLF-4 overexpression markedly reduced the PAI-1 expression and inhibited the TGF-β-induced EMT in LA-4 cells. In conclusion, our study confirmed the downregulation of KLF-4 in the TGF-β-induced EMT in LA-4 cells. And the KLF-4 overexpression significantly reduced the TGF-β-induced PAI-1 and thus inhibited the TGF-β-induced EMT in mouse lung epithelial LA-4 cells. It implies that KLF-4 might be a promising target for effective control of the pulmonary fibrosis.