title: Regulatory mechanisms of TGF-β1-induced fibrogenesis of human alveolar epithelial cells.
abstract: Pulmonary fibrosis is characterized by an extensive activation of fibrogenic cells and deposition of extracellular matrix (ECM). Transforming growth factor (TGF)-β1 plays a pivotal role in the pathogenesis of pulmonary fibrosis, probably through the epithelial- to-mesenchymal transition (EMT) and ECM production. The present study investigates potential mechanism by which TGF-β1 induces EMT and ECM production in the fibrogenesis of human lung epithelial cells during pulmonary fibrosis. The expression of EMT phenotype and other proteins relevant to fibrogenesis were measured and the cell bio-behaviours were assessed using Cell-IQ Alive Image Monitoring System. We found that TGF-β1-induced EMT was accompanied with increased collagen I deposition, which may be involved in the regulation of connective tissue growth factor (CTGF) and phosphoinositide 3-kinase (PI3K) signalling pathway. Treatment with PI3K inhibitors significantly attenuated the TGF-β1- induced EMT, CTGF expression and collagen I synthesis in lung epithelial cells. The interference of CTGF expression impaired the basal and TGF-β1-stimulated collagen I deposition, but did not affect the process of EMT. Our data indicate that the signal pathway of TGF-β1/PI3K/CTGF plays an important role in the fibrogenesis of human lung epithelial cells, which may be a novel therapeutic approach to prevent and treat pulmonary fibrosis.
authors.affiliation: Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Zhongshan Hospital Institute of Clinical Science of Fudan University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shi
authors.affiliation: Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Zhongshan Hospital Institute of Clinical Science of Fudan University, Shanghai, China.
authors.forename: Nian
authors.initials: N
authors.lastname: Dong
authors.affiliation: Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Zhongshan Hospital Institute of Clinical Science of Fudan University, Shanghai, China.
authors.forename: Xiaocong
authors.initials: X
authors.lastname: Fang
authors.affiliation: Zhongshan Hospital, Shanghai Institute of Clinical Bioinformatics, Fudan University Center for Clinical Bioinformatics, Zhongshan Hospital Institute of Clinical Science of Fudan University, Shanghai, China. xiangdong.wang@clintransmed.org.
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005355:Fibrosis; D006801:Humans; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; D055513:Connective Tissue Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D053773:Transforming Growth Factor beta1
keywords: CTGF; EMT; PI3K; TGF-β1; fibrosis