Targeting EZH1 and EZH2 contributes to the suppression of fibrosis-associated genes by miR-214-3p in cardiac myofibroblasts.
The role of microRNA-214-3p (miR-214-3p) in cardiac fibrosis was not well illustrated. The present study aimed to investigate the expression and potential target of miR-214-3p in angiotensin II (Ang-II)-induced cardiac fibrosis. MiR-214-3p was markedly decreased in the fibrotic myocardium of a mouse Ang-II infusion model, but was upregulated in Ang-II-treated mouse myofibroblasts. Cardiac fibrosis was shown attenuated in Ang-II-infused mice received tail vein injection of miR-214-3p agomir. Consistently, miR-214-3p inhibited the expression of Col1a1 and Col3a1 in mouse myofibroblasts in vitro. MiR-214-3p could bind the 3'-UTRs of enhancer of zeste homolog 1 (EZH1) and -2, and suppressed EZH1 and -2 expressions at the transcriptional level. Functionally, miR-214-3p mimic, in parallel to EZH1 siRNA and EZH2 siRNA, could enhance peroxisome proliferator-activated receptor-γ (PPAR-γ) expression and inhibited the expression of Col1a1 and Col3a1 in myofibroblasts. In addition, enforced expression of EZH1 and -2, and knockdown of PPAR-γ resulted in the increase of Col1a1 and Col3a1 in myofibroblasts. Moreover, the NF-κB signal pathway was verified to mediate Ang-II-induced miR-214-3p expression in myofibroblasts. Taken together, our results revealed that EZH1 and -2 were novel targets of miR-214-3p, and miR-214-3p might be one potential miRNA for the prevention of cardiac fibrosis.
Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Wen-Si
WS
Zhu
Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.|Southern Medical University, Guangzhou, China.
Chun-Mei
CM
Tang
Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Zhen
Z
Xiao
Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Jie-Ning
JN
Zhu
Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Qiu-Xiong
QX
Lin
Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Yong-Heng
YH
Fu
Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.|Southern Medical University, Guangzhou, China.
Zhi-Qin
ZQ
Hu
Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.|School of Medicine, South China University of Technology, Guangzhou, China.
Zhuo
Z
Zhang
Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Min
M
Yang
The Libin Cardiovascular Institute of Alberta, Department of Biochemistry & Molecular Biology, The University of Calgary, Calgary, Canada.
Xi-Long
XL
Zheng
Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Shu-Lin
SL
Wu
Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou, China.|Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Zhi-Xin
ZX
Shan
D020413:3' Untranslated Regions; D000804:Angiotensin II; D000818:Animals; D001665:Binding Sites; D009202:Cardiomyopathies / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D005786:Gene Expression Regulation; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D058628:Myofibroblasts / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection
D020413:3' Untranslated Regions; C000609875:COL3A1 protein, mouse; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D035683:MicroRNAs; C534781:Mirn214 microRNA, mouse; D016328:NF-kappa B; D009841:Oligonucleotides; D047495:PPAR gamma; D000804:Angiotensin II; D000071221:Enhancer of Zeste Homolog 2 Protein; C498408:Ezh1 protein, mouse; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2
EZH1; EZH2; Pathology Section; cardiac fibrosis; cardiac myofibroblast; microRNA-214-3p