Resveratrol inhibits pulmonary fibrosis by regulating miR-21 through MAPK/AP-1 pathways

Publication date: September 2018
Source:Biomedicine & Pharmacotherapy, Volume 105
Author(s): Jing Wang, Fang He, Lingqiang Chen, Qin Li, Song Jin, Hongmei Zheng, Jun Lin, Hong Zhang, Sha Ma, Jian Mei, Juan Yu
ObjectiveTo explore the molecular mechanism of Res in regulation of pulmonary fibrosis (PF).MethodsRats were injected with bleomycin (BLM) to establish a PF model and treated with resveratrol (Res) and/or miR-21 agomir. After 14 days, lung tissues were collected for Hematoxylin-eosin and Masson's staining, and real-time quantitative polymerase chain reaction and Western blot were performed to detect fibrosis-related protein expression and the activation of the TGF-β1/Smad pathway. In vitro, MRC-5 cells were pretreated with TGF-β1, Res, and/or miR-21 agomir. After 48 h, total soluble collagen was detected with a Sircol Soluble Collagen Assay. Subsequently, a miR-21 mimic was transfected into MRC-5 cells, and a luciferase reporter assay was employed to verify whether miR-21 targeted Smad7.ResultsRes reversed the increased levels of miR-21 induced by BLM and alleviated serious PF symptoms, but agomiR-21 treatment effectively impaired the above manifestations. In vivo, miR-21 inhibited the decreases of TGF-β1 and p-Smad2/3 that were induced by Res. In vitro, miR-21 significantly disrupted the positive effect of Res on TGF-β-induced collagen deposition, as well as the levels of Fn, α-SMA, p-Smad2, and Smad7. In addition, Smad7 was found to be a direct target of miR-21-5p. TGF-β stimulation led to an enormous increase in p-c-Jun, c-Jun, and c-Fos, which were significantly reduced by Res. Finally, miR-21 sharply reduced the increased phosphorylation levels of ERK, JNK and p38 that were induced by Res.ConclusionRes inhibits BLM-induced PF by regulating miR-21 through MAPK/AP-1 pathways.

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