Related Experiment Video
Updated: Feb 9, 2026
Oropharyngeal Administration of Bleomycin in the Murine Model of Pulmonary Fibrosis
Published on: May 9, 2025
Resveratrol inhibits pulmonary fibrosis by regulating miR-21 through MAPK/AP-1 pathways
Jing Wang1, Fang He1, Lingqiang Chen2
1Department of Rheumatology, The First People's Hospital of Yunnan Province, Kunming 650034, Yunnan Province, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming 650034, Yunnan Province, China.
Objective:
To explore the molecular mechanism of Res in regulation of pulmonary fibrosis (PF).
Methods:
Rats 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.
Results:
Res 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.
Conclusion:
Res inhibits BLM-induced PF by regulating miR-21 through MAPK/AP-1 pathways.
Insights
Resveratrol (Res) inhibits pulmonary fibrosis (PF) by downregulating miR-21, thereby modulating the MAPK/AP-1 pathway. This study elucidates Res
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Pulmonary fibrosis (PF) is a progressive and often fatal lung disease characterized by excessive extracellular matrix deposition.
- The molecular mechanisms underlying PF pathogenesis are complex and involve intricate signaling pathways.
- Resveratrol (Res), a natural polyphenol, has shown potential therapeutic effects in various diseases, including PF.
Purpose of the Study:
- To investigate the molecular mechanisms by which Resveratrol (Res) regulates pulmonary fibrosis (PF).
- To explore the role of miR-21 in Resveratrol's antifibrotic effects.
- To elucidate the involvement of the TGF-β1/Smad and MAPK/AP-1 signaling pathways.
Main Methods:
- Established a bleomycin (BLM)-induced pulmonary fibrosis model in rats.
- Treated rats with Resveratrol (Res) and/or miR-21 agomir.
- Performed histological analysis (H&E, Masson's staining), RT-qPCR, and Western blotting to assess fibrosis and protein expression.
- Utilized in vitro cell culture (MRC-5 cells) with TGF-β1 stimulation, Resveratrol treatment, and miR-21 mimic transfection.
- Quantified collagen deposition using Sircol Soluble Collagen Assay.
- Verified miR-21 targeting of Smad7 via luciferase reporter assay.
Main Results:
- Resveratrol treatment reversed BLM-induced increases in miR-21 and alleviated PF symptoms in vivo.
- miR-21 dysregulated the antifibrotic effects of Resveratrol, inhibiting TGF-β1 and p-Smad2/3 expression.
- In vitro, miR-21 disrupted Resveratrol's beneficial effects on collagen deposition and fibrotic markers (Fn, α-SMA).
- Smad7 was identified as a direct target of miR-21-5p.
- Resveratrol reduced TGF-β1-induced activation of the MAPK pathway (ERK, JNK, p38) and AP-1 components (c-Jun, c-Fos).
Conclusions:
- Resveratrol inhibits bleomycin-induced pulmonary fibrosis by regulating miR-21.
- The antifibrotic mechanism of Resveratrol involves the modulation of miR-21 and downstream signaling pathways, including MAPK/AP-1.
- Targeting miR-21 may represent a therapeutic strategy for pulmonary fibrosis.
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