Open AccessPI3K/Akt signaling is involved in the pathogenesis of bleomycin-induced pulmonary fibrosis via regulation of epithelial-mesenchymal transition
Author(s) -
Zhang Xiao-ling,
Rongge Xing,
Liang Chen,
Chunrong Liu,
Miao Zhang
Publication year - 2016
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2016.5960
Subject(s) - protein kinase b , pi3k/akt/mtor pathway , epithelial–mesenchymal transition , pulmonary fibrosis , idiopathic pulmonary fibrosis , bleomycin , cancer research , fibrosis , bronchoalveolar lavage , myofibroblast , pathology , medicine , signal transduction , lung , biology , microbiology and biotechnology , cancer , chemotherapy , metastasis
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.