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Inhibition of miR-182-5p attenuates pulmonary fibrosis via TGF-β/Smad pathway
1Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Abstract:
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with high morbidity and mortality. miR-182-5p is overexpressed in several fibrosis-related diseases but its effect in pulmonary fibrosis has not been reported yet. To investigate the function of miR-182-5p in pulmonary fibrosis, we established bleomycin (BLM)-induced fibrotic mice model and transforming growth factor-β1 (TGF-β1)-treated human embryonic lung fibroblasts model. In this study, miR-182-5p was highly expressed in pulmonary tissues of BLM-induced fibrotic mice. The content of hydroxyproline and TGF-β1 was decreased by downregulating the expression of miR-182-5p, indicating that fibrosis was alleviated in mice treated with Lentivirus-anti-miR-182-5p.Quantification of fibrosis-related proteins demonstrated that downregulation of miR-182-5p inhibited the expression of profibrotic proteins (fibronectin, α-smooth muscle actin, p-Smad2/p-Smad3) as well as enhanced the level of Smad7. In vitro assays validated that miR-182-5p was induced by TGF-β1 with the function of promoting fibrosis. In dual-luciferase reporter assay, Smad7 was demonstrated to be negatively regulated by miR-182-5p. Moreover, the effect of knocking down miR-182-5p on inhibiting fibrosis was achieved by upregulating the expression of Smad7. Therefore, miR-182-5p can be regarded as a biomarker of IPF and its inhibition may be a promising therapeutic approach in treating IPF.
Insights
MicroRNA-182-5p (miR-182-5p) promotes idiopathic pulmonary fibrosis (IPF). Inhibiting miR-182-5p alleviates lung fibrosis by upregulating Smad7, suggesting it as a potential therapeutic target for IPF.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Biochemistry
Background:
- Idiopathic pulmonary fibrosis (IPF) is a severe lung disease with limited treatment options.
- MicroRNA-182-5p (miR-182-5p) is implicated in other fibrotic conditions but its role in IPF remains unclear.
Purpose of the Study:
- To investigate the role of miR-182-5p in the pathogenesis of pulmonary fibrosis.
- To explore the potential of targeting miR-182-5p as a therapeutic strategy for IPF.
Main Methods:
- Established bleomycin (BLM)-induced pulmonary fibrosis in mice and transforming growth factor-β1 (TGF-β1)-treated human lung fibroblasts.
- Assessed fibrosis markers (hydroxyproline, profibrotic proteins) and miR-182-5p expression.
- Utilized lentivirus-mediated downregulation of miR-182-5p and dual-luciferase reporter assays.
Main Results:
- miR-182-5p was significantly upregulated in fibrotic lung tissues.
- Downregulation of miR-182-5p reduced hydroxyproline and TGF-β1 levels, alleviating fibrosis.
- Inhibition of miR-182-5p decreased profibrotic proteins (fibronectin, α-SMA) and increased Smad7, which was identified as a direct target.
Conclusions:
- miR-182-5p promotes pulmonary fibrosis by suppressing Smad7.
- miR-182-5p is a potential biomarker for IPF.
- Inhibiting miR-182-5p represents a promising therapeutic avenue for treating IPF.
