MicroRNA-21 protects cardiomyocytes from tumor necrosis factor-α induced apoptosis in vitro via modulating PTEN/AKT/FOXO3a pathway
10.3760/cma.j.issn.0253-3758.2013.02.012
- VernacularTitle:微小RNA-21对乳鼠心肌细胞凋亡及磷酸脂酶-张力蛋白同源物/丝氨酸/苏氨酸激酶/叉头蛋白3a信号传导通路的影响
- Author:
Yan TANG
1
;
Meng-Hong WANG
Author Information
1. 南华大学医学院第一附属医院心内科
- Keywords:
Myocytes,cardiac;
Apoptosis;
MicroRNAs;
Signal transduction
- From:
Chinese Journal of Cardiology
2013;41(2):135-142
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of microRNA-21 on tumor necrosis factor(TNF)-α induced cardiomyocytes apoptosis and the association with PTEN/AKT/FOXO3a signaling pathway.Methods Neonatal cardiomyocytes were isolated and cultured in vitro.Cardiomyocytes apoptosis was induced by TNF-α (10 ng/ml for 24 h) and examined by the cardiomyocytes apoptotic index.Eukaryotic expression vector for lenti-microRNA-21 was established and then transferred into the cardiomyocytes.MicroRNA-21 and PTEN mRNA were examined by qRT-PCR.Intracellular signal molecules,such as the expression of PTEN,phosphorylated PTEN,AKT,phosphorylated AKT (pAKTser473、pAKTThr308),FOXO3a,phosphorylated FOXO3a and FasL were detected by Western blot.Results MicroRNA-21 reduced TNF-α induced cardiomyocytes apoptosis [(23.42 ± 1.98)％ vs.(78.37 ±2.03)％,P ＜0.05].TNF-α downregulated the expression of microRNA-21 and upregulated the mRNA and protein expressions of PTEN.Phosphorylation of PTEN,AKT and FOXO3a was enhanced in cardiomyocytes transfected with lenti-microRNA-21 (P ＜ 0.05).TNF-α also significantly activated the phosphorylation of PTEN,AKT and FOXO3a (P ＜0.05).Compared with cardiomyocytes treated with TNF-α (10 ng/ml),the phosphorylation of PTEN,AKT and FOXO3a as well as expression of pPTEN,pAKTser473,pFOXO3a and FasL were significantly suppressed in cardiomyocytes treated with lenti-microRNA-21 and TNF-o (P ＜ 0.05).Total AKT and FOXO3a were similar among all groups (P ＞ 0.05).Conclusions MicroRNA-21 could protect cardiomyocytes from TNF-α-induced apoptosis through PTEN/AKT/FOXO3a pathway,which might serve as a new therapy option for various cardiovascular diseases in the future.
