MiR-125b regulates SFRP5 expression to promote growth and activation of cardiac fibroblasts.
Myocardial fibrosis (MF), which typically occurs after a myocardial infarction (MI), is a major factor involved in the process of ventricular remodeling and subsequent progression to heart failure. Current studies have found that various microRNAs (miRNAs), such as miR-125b, play an important role in this process. However, few studies have investigated the specific mechanism of miR-125b. Transfection of miR-125b mimics into cardiac fibroblasts (CFs) resulted in significantly increased expression of the myofibroblast marker alpha-smooth muscle actin (α-SMA) and vinculin by Western blot analysis, while transfection of miR-125b inhibitors resulted in the opposite effect. Analysis of putative CF target genes for miR-125b revealed that miR-125b specifically inhibits expression of secreted frizzled-related protein 5 (SFRP5). SFRP5 inhibited expression of α-SMA and collagen I and III in CFs, while miR-125b promoted the expression of these proteins. Cotransfection of the SFRP5 overexpression vector and miR-125b mimics did not result in significant upregulation of SFRP5 expression or downregulation of α-SMA and collagen I and III. Further analysis revealed that miR-125b promotes the proliferation and migration of CFs and inhibits their apoptosis, while SFRP5 exhibits the opposite effects. These results indicate that miR-125b can regulate SFRP5 expression and thus influence the growth and activation of CFs. Hence, this study provides important insight into possible approaches for the prevention and treatment of MF after an MI.
Shandong University School of Medicine, Jinan, 250012, Shandong, China.|Department of Cardiology, Weihai Central Hospital, Weihai, 264423, Shandong, China.
Zi-Dong
ZD
Bie
Shandong University School of Medicine, Jinan, 250012, Shandong, China.|Department of Geratology, Yantai Yuhuangding Hospital, Yantai, 264000, Shandong, China.
Li-Ye
LY
Sun
Department of Cardiology, Weihai Central Hospital, Weihai, 264423, Shandong, China.
Chuan-Liang
CL
Geng
Emergency Department, Weihai Central Hospital, Weihai, 264423, Shandong, China.
Qing-Guo
QG
Meng
Department of Cardiology, Weihai Central Hospital, Weihai, 264423, Shandong, China.
Xiao-Jing
XJ
Lin
Department of Cardiology, Weihai Central Hospital, Weihai, 264423, Shandong, China.
Yu-Feng
YF
Wang
Department of Cardiology, Weihai Central Hospital, Weihai, 264423, Shandong, China.
Xue-Ban
XB
Wang
Department of Cardiology, Yantai Yuhuangding Hospital, 20# Yuhuangding East Road, Zhifu District, Yantai, 264000, Shandong, China. chenxiuhua126@163.com.
Jun
J
Yang
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D017209:Apoptosis / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D024061:Collagen Type III / Q000096:biosynthesis; D004719:Endomyocardial Fibrosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005136:Eye Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism*; D014162:Transfection; D000094742:Secreted Frizzled-Related Proteins
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D024042:Collagen Type I; D024061:Collagen Type III; D005136:Eye Proteins; D008565:Membrane Proteins; D035683:MicroRNAs; C541116:ACTA2 protein, human; C531888:MIRN125 microRNA, human; C118511:SFRP5 protein, human; D000094742:Secreted Frizzled-Related Proteins
SFRP5; cardiac fibroblasts; miR-125b; myocardial infarction