title: PI3K/Akt signaling is involved in the pathogenesis of bleomycin‑induced pulmonary fibrosis via regulation of epithelial‑mesenchymal transition.
abstract: Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by chronic inflammation, fibroblast proliferation and extracellular matrix deposition. However, the molecular and cellular mechanisms underlying the pathogenesis of pulmonary fibrosis remain to be fully elucidated. The contribution of the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt) pathway in fibrotic processes remains to be investigated. The aim of the present study was to investigate the role of the PI3K/Akt pathway in pulmonary fibrosis. A rat model of pulmonary fibrosis was induced by intratracheal administration of bleomycin (BLM), and a specific PI3K/Akt inhibitor, LY294002, was used to assess the role of the PI3K/Akt pathway in fibrogenesis. The inflammatory and fibrotic alterations in the lung tissues were evaluated using histological staining and the hydroxyproline assay. In addition, the concentration of cytokines in bronchoalveolar lavage fluid and the expression of Akt, phosphorylated (p‑)Akt, epithelial cadherin, α smooth muscle actin and vimentin in lung tissues. The data demonstrated that an increase in the expression levels of p‑Akt was involved in the progression of pulmonary fibrosis and contributed to fibrogenesis. Administration of the Akt inhibitor significantly attenuated inflammation and fibrosis, which was accompanied by a reversal of lung fibrosis‑associated epithelial‑mesenchymal transition. Taken together, these observations suggest that the PI3K/Akt pathway serves a central role in the pathophysiology of lung fibrosis, and is a promising therapeutic target.
authors.affiliation: Department of Pathology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.
authors.forename: Rong-Ge
authors.initials: RG
authors.lastname: Xing
authors.affiliation: Department of Oncology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pathology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.
authors.forename: Chun-Rong
authors.initials: CR
authors.lastname: Liu
authors.affiliation: Department of Pathology, Cangzhou Central Hospital, Cangzhou, Hebei 061001, P.R. China.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Miao
mesh_terms: D000818:Animals; D015415:Biomarkers; D001761:Bleomycin / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D047428:Protein Kinase Inhibitors; D001761:Bleomycin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt