细胞周期蛋白依赖激酶6
细胞凋亡
脂多糖
体内
炎症
体外
荧光素酶
NF-κB
化学
癌症研究
药理学
医学
免疫学
细胞周期蛋白D1
生物
细胞周期
转染
生物化学
生物技术
基因
作者
Lap-Fai Yu,Guoqiang Sun,Luqiang Wang
标识
DOI:10.1007/s00011-021-01535-1
摘要
This study aimed to investigate the relationship between miR-21 and lipopolysaccharide (LPS)-induced myocardial injury and its molecular and regulatory mechanisms.We constructed LPS-mediated myocardial injury model using C57BL/6J mice and H9c2 cells. In-vivo, in-vitro, RIP and dual-luciferase reporter assays were used to determine the effect of miR-21 on myocardial injury.In-vivo and in-vitro results showed that the expression of miR-21 was increased in LPS-treated H9c2 cells and myocardial tissues of mice, and the pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) and NF-κB pathway were activated in LPS-treated H9c2 cells. Besides, the B-cell lymphoma-2 (Bcl-2) and cyclin-dependent kinase 6 (CDK6) expression levels decreased, while Bax and cleaved caspase 9 levels increased in LPS-treated H9c2 cells. Inhibition of miR-21 could suppress LPS-induced apoptosis, inflammatory reactions and NF-κB activation to attenuate LPS-induced myocardial injury in H9c2 cells, and effectively improve survival of mice with sepsis. Most importantly, Bcl-2 and CDK6 were found to be the direct target of miR-21 using dual-luciferase reporter and RNA immunoprecipitation assays. Further gain-of-function assay demonstrated that Bcl-2 or CDK6 over-expression promoted the protective effects of miR-21 inhibitor on LPS-mediated myocardial cells.Our findings revealed that the down-regulation or antagonism of miR-21 protects myocardial cells against LPS-induced apoptosis and inflammation through up-regulating Bcl-2 and CDK6 expression, which provided a new insight for prevention and treatment of myocardial injury.
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