miR-199a-5p enhances expression of myocardial fibrosis-related genes by targeting SIRT1
10.3969/j.issn.1000-4718.2017.10.008
- VernacularTitle:微小RNA-199a-5p通过靶向SIRT1促进心肌纤维化相关基因表达
- Author:
Zhuo ZHANG
1
;
ning Jie ZHU
;
Zhen XIAO
;
qin Zhi HU
;
mei Chun TANG
;
heng Yong FU
;
xiong Qiu LIN
;
lin Shu WU
;
Chang DU
;
xin Zhi SHAN
Author Information
1. 华南理工大学医学院
- Keywords:
Myocardial fibrosis;
Fibroblasts;
MicroRNA-199a-5p;
Silent information regulator 1
- From:
Chinese Journal of Pathophysiology
2017;33(10):1781-1787
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the role of microRNA (miR)-199a-5p in myocardial fibrosis and the potential target of miR-199a-5p.METHODS:C57BL/6 mouse cardiac fibroblasts were isolated and cultured for cellular experimen-tal study.Dual-luciferase reporter assay was performed to confirm the interaction between miR-199a-5p and the 3'-untrans-lated region (3'-UTR) of silent information regulator 1 (SIRT1).The expression of SIRT1 and fibrosis markers collagen (Col) 1a1, Col3a1 and α-smooth muscle actin (α-SMA) at mRNA and protein levels was determined by RT-qPCR and Western blot, respectively.RESULTS:The expression levels of miR-199a-5p, Col1a1, Col3a1 andα-SMA were marked-ly increased in cardiac fibroblasts after treatment with angiotensin Ⅱ(AngⅡ).The over-expression of miR-199a-5p signif-icantly increased the expression of Col1a1, Col3a1 andα-SMA in cardiac fibroblasts.Moreover, the results of dual-lucifer-ase reporter assay revealed that miR-199a-5p interacted with the 3'-UTR of SIRT1.miR-199a-5p inhibited SIRT1 expres-sion at post-transcriptional level.Meanwhile, miR-199a-5p mimic, in parallel to SIRT1 siRNA, inhibited SIRT1 expres-sion, increased the expression of Col1a1, Col3a1 and α-SMA in cardiac fibroblasts.Inactivation of NF-κB signaling con-tributed to the decrease in miR-199a-5p in Ang II-treated cardiac fibroblasts .CONCLUSION:SIRT1 is a target gene of miR-199a-5p, which mediates the pro-fibrotic effect of miR-199a-5p on cardiac fibroblasts .
