Research Papers:

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

Zhen Chen, Hua-Sheng Ding, Xin Guo, Jing-Jing Shen, Di Fan, Yan Huang and Cong-Xin Huang _

PDF  |  HTML  |  How to cite

Oncotarget. 2018; 9:22047-22057. https://doi.org/10.18632/oncotarget.25173

Metrics: PDF 1369 views  |   HTML 2131 views  |   ?  


Zhen Chen1,2,3, Hua-Sheng Ding1,2,3, Xin Guo1,2,3, Jing-Jing Shen1,2,3, Di Fan1,2,3, Yan Huang1,2,3 and Cong-Xin Huang1,2,3

1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, PR China

2Institute of Cardiovascular Diseases, Wuhan University, Wuhan 430060, PR China

3Hubei Key Laboratory of Cardiology, Wuhan 430060, PR China

Correspondence to:

Cong-Xin Huang, email: [email protected]

Keywords: myocardial fibrosis; cardiac fibroblasts; miRNA-33; matrix metalloproteinase 16; p38 MAPK signaling pathway

Received: July 31, 2017     Accepted: January 20, 2018     Published: April 24, 2018


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 25173