MiR-33 promotes myocardial fibrosis by inhibiting MMP16 and stimulating p38 MAPK signaling

Oncotarget
Zhen ChenCong-Xin Huang

Abstract

Myocardial fibrosis occurs in the late stages of many cardiovascular diseases, and appears to be stimulated by various microRNAs (miRNAs). We previously found that miR-33 may stimulate cardiac remodeling. Here, we examined the involvement of miR-33 in myocardial fibrosis. Proximal left coronary descending artery occlusion was performed in rat, and antagomiR-33a was injected. Primary cardiac fibroblasts were cultured and transfected with miR-33a mimics and inhibitors. miR-33a levels were increased in the rat after surgery, and collagen deposition and heart fibrosis were observed in vivo. Inhibition of miR-33a suppressed fibroblast proliferation, reduced the mRNA and protein levels of collagen-related markers in vitro and in vivo, and rescued the histological damage in vivo. A dual-luciferase reporter system showed that matrix metalloproteinase 16 (MMP16) gene was the direct target of MiR-33a. These results suggest that miR-33 promoted myocardial fibrosis by inhibiting MMP16 and stimulating p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. MiR-33 may act as a novel therapeutic target for treating myocardial fibrosis.

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Citations

Jan 18, 2019·Journal of Cardiovascular Development and Disease·Adriana M Rodriguez, Viravuth P Yin
Feb 23, 2019·Expert Review of Gastroenterology & Hepatology·Agostino Di CiaulaPiero Portincasa
Feb 13, 2021·Life Sciences·Xuping LiYuanyuan Cheng
Mar 20, 2019·Archives of Oral Biology·Toshiki YonedaManabu Morita
Oct 16, 2020·Journal of Receptor and Signal Transduction Research·Wang XingHanbo Tang
Jul 4, 2021·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Jiang LiuJuanjuan Jiang

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Methods Mentioned

BETA
transfection
PCR
electrophoresis

Software Mentioned

SPSS
Image J
TargetScan

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