MicroRNA-99b-5p Aggravates Cardiomyocyte Hypertrophy by Down-regulating Fgf21
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2022.0204
- VernacularTitle:MicroRNA-99b-5p通过抑制成纤维细胞生长因子21表达促进心肌细胞肥大
- Author:
Li-wen CHEN
1
;
Jing GUO
2
;
Ze-run CHEN
3
;
Jie-ning ZHU
1
;
Jin-dong XU
1
;
Hui-ming GUO
1
;
Zhi-xin SHAN
1
;
Sheng WANG
1
Author Information
1. Guangdong Cardiovascular Institute//Guangdong Provincial People’s Hospital // Guangdong Academy of Medical Sciences， Guangzhou 510080， China
2. School of Medicine， South China University of Technology， Guangzhou 510006， China
3. The Second School of Clinical Medicine， Southern Medical University， Guangzhou 510280， China.
- Publication Type:Journal Article
- Keywords:
cardiomyocyte hypertrophy;
miR-99b-5p;
fibroblast growth factor 21
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2022;43(2):192-202
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the role of microRNA-99b-5p （miR-99b-5p） in cardiomyocyte hypertrophy and the related mechanism involved. MethodsThe expression of miR-99b-5p in myocardium was detected by real-time quantitative PCR（RT-qPCR）in the myocardium of patients with heart failure（HF）and healthy controls， as well as in the myocardium of mouse model of transverse aortic restriction （TAC）-induced cardiac hypertrophy. Phalloidin-iFluor 647 staining was used to show the size of neonatal mouse ventricular cardiomyocytes（NMVCs）after AngⅡ treatment. MiR-99b-5p expression was determined by RT-qPCR in AngⅡ-treated NMVCs. After transfection with miR-99b-5p mimic， the expression of cardiac hypertrophy-associated genes and Fgf21 in NMVCs was detected by RT-qPCR and Western blot assay， respectively. We identified the interaction between miR-99b-5p and the 3’UTR of Fgf21 mRNA by dual luciferase reporter assay. The recombinant Ffg21 adenovirus（rAd-Fgf21）and rAd-Sod2 were used to infect NMVCs， and the expression of β-MHC， ANP， FGF21 and SOD2 was detected by Western blot assay. We knocked down Fgf21 and Sod2 in NMVCs to investigate the role of FGF21/Sod2 axis in miR-99b-5p-regulated NMVC hypertrophy. ResultsMiR-99b-5p expression was elevated in the myocardium of HF patients and TAC-operated mice， and in AngⅡ-treated NMVCs （P＜0.01， respectively）. MiR-99b-5p promoted the expression of hypertrophy-related genes in NMVCs （P＜0.01）. Results of dual luciferase reporter gene assay revealed the interaction between miR-99b-5p and Fgf21 mRNA. MiR-99b-5p down-regulated the expression of Fgf21 and the down-stream gene of Sod2（ P＜0.01）. Overexpression of FGF21 or SOD2 could inhibit NMVC hypertrophy and effectively reversed the pro-hypertrophy effect of miR-99b-5p on NMVCs （P＜0.05， respectively）. ConclusionMiR-99b-5p is up-regulated in the hypertrophic myocardium and enhances cardiomyocyte hypertrophy via suppressing Fgf21/Sod2 axis.
