Open AccessSulindac has strong antifibrotic effects by suppressing STAT 3‐related miR‐21
Author(s) -
Zhou Xue,
Li YouJie,
Gao ShuYan,
Wang XiaoZhi,
Wang PingYu,
Yan YunFei,
Xie ShuYang,
Lv ChangJun
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12506
Subject(s) - sulindac , stat , bleomycin , chemistry , a549 cell , pulmonary fibrosis , cancer research , fibrosis , pathogenesis , stat protein , stat1 , pharmacology , signal transduction , biology , medicine , cell , stat3 , biochemistry , chemotherapy , nonsteroidal
Pulmonary fibrosis ( PF ) is a disease with an unknown cause and a poor prognosis. In this study, we aimed to explore the pathogenesis of PF and the mechanism of sulindac in attenuating bleomycin ( BLM )‐induced PF . The rat PF model was induced by BLM and verified through histological studies and hydroxyproline assay. The severity of BLM ‐induced PF in rats and other effects, such as the extent of the wet lung to bw ratios, thickening of alveolar interval or collagen deposition, was obviously ameliorated in sulindac‐treated rat lungs compared with BLM ‐induced lungs. Sulindac also reversed the epithelial mesenchymal transition ( EMT ) and inhibited the PF process by restoring the levels of E‐cadherin and α‐smooth muscle actin ( SMA ) in A549 cells. Our results further demonstrated that the above effects of sulindac might be related to regulating of interferon gamma ( IFN ‐γ) expression, which further affects signal transducers and activators of transcription 3 ( STAT 3) and phosphorylated STAT 3 (p‐ STAT 3) levels. Moreover, higher miR‐21 levels with the decreased E‐cadherin and increased α‐ SMA expressions were found in transforming growth factor‐β1‐treated A549 cells, which can be reversed by sulindac. Collectively, our results demonstrate that by decreasing IFN ‐γ‐induced STAT 3/p‐ STAT 3 expression to down‐regulate miR‐21, sulindac could significantly reverse EMT in A549 cells and prevent BLM ‐induced PF .