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Inhibition of miR-182-5p attenuates pulmonary fibrosis via TGF-β/Smad pathway
被引：30
|作者：
Chen, Y.
[1
]
Zhang, Q.
[1
]
Zhou, Y.
[1
]
Yang, Z.
[1
]
Tan, M.
[1
]
机构：
[1] China Med Univ, Shengjing Hosp, Dept Resp Med, Shenyang 110022, Peoples R China
基金：
中国国家自然科学基金;
关键词：
Idiopathic pulmonary fibrosis;
miR-182-5p;
Smad7;
TGF-beta;
Smad signaling pathway;
HEPATIC STELLATE CELLS;
RENAL FIBROSIS;
BETA;
EXPRESSION;
MICRORNAS;
DISEASE;
D O I：
10.1177/0960327119895549
中图分类号：
R99 [毒物学（毒理学）];
学科分类号：
100405 ;
摘要：
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-beta 1 (TGF-beta 1)-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-beta 1 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, alpha-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-beta 1 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.
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页码：683 / 695
页数：13
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