Inhibition of miR-182-5p attenuates pulmonary fibrosis via TGF-β/Smad pathway
| Autor: | Yang Zh, Yi-shu Zhou, Qiang Zhang, Yingying Chen, Mingqi Tan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis Down-Regulation Smad Proteins Toxicology Bleomycin 03 medical and health sciences chemistry.chemical_compound Idiopathic pulmonary fibrosis Mice 0302 clinical medicine Downregulation and upregulation Fibrosis Transforming Growth Factor beta Pulmonary fibrosis Medicine Animals Humans Lung biology business.industry General Medicine Fibroblasts medicine.disease Idiopathic Pulmonary Fibrosis Fibronectins Fibronectin Disease Models Animal MicroRNAs 030104 developmental biology medicine.anatomical_structure chemistry 030220 oncology & carcinogenesis biology.protein Cancer research Biomarker (medicine) business Signal Transduction |
| Zdroj: | Humanexperimental toxicology. 39(5) |
| ISSN: | 1477-0903 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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