title: Krüppel-Like Factor 4 Inhibits the Transforming Growth Factor-β1-Promoted Epithelial-to-Mesenchymal Transition via Downregulating Plasminogen Activator Inhibitor-1 in Lung Epithelial Cells.
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.
authors.affiliation: Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Sun
authors.affiliation: Division of Respiratory Disease, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D058258:Serpin E2 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D058258:Serpin E2; C511869:Serpine2 protein, mouse
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