ERRα通过调控肌钙蛋白I表达促进心肌细胞成熟的机制  

Role of ERRαin regulation of isoform switch of troponin I during cardiomyocytes maturation

作　　者：陈聪[1] 杨月星 黄安芳 付虎[1] CHEN Cong;YANG Yuexing;HUANG Anfang;FU Hu(Department of Pediatrics,Chengdu First People's Hospital,Chengdu 610016,China;The First Affiliated Hospital of Southwest Medical University Luzhou 646000,Sichuan,China)

机构地区：[1]成都市第一人民医院,四川成都610016 [2]西南医科大学附属第一医院,四川泸州646000

出　　处：《西部医学》2021年第9期1311-1315,共5页Medical Journal of West China

基　　金：四川省科技计划项目(2019YJ0540)。

摘　　要：目的探讨雌激素受体α(ERRα)通过调控肌钙蛋白I表达促进心肌细胞成熟过程中的调控机制。方法以胎龄14.5天(E14.5组)、17.5天(E17.5组)、新生(NB组)及出生后2周(P2W组)、出生后4周(P4W组)SPF级c57小鼠为研究对象。利用Q-PCR及Western blot检测ERRα、胚胎型肌钙蛋白I(ssTnI)、心肌肌钙蛋白I(cTnI)、肌球蛋白重链α(αMHC)及肌球蛋白重链β(βMHC)在mRNA及蛋白水平的时空表达规律。利用染色质免疫共沉淀(ChIP)技术检测ssTnI、cTnI、αMHC及βMHC启动子区域乙酰化水平以及ERRα与ssTnI、cTnI、αMHC及βMHC启动子结合水平。结果ERRα、cTnI及αMHC在心脏发育过程中表达水平逐渐升高,其中ERRα和cTnI在生后2周达峰值(P<0.05),后维持在稳定水平;αMHC则在P4W组表达水平最高,与其他各组比较差异均有统计学意义(P<0.05);E14.5组心脏中ssTnI和βMHC表达水平较其余各组明显升高(P<0.05);cTnI启动子乙酰化水平逐渐升高,在P2W组达高峰,同时ERRα与之启动子结合水平与cTnI表达水平一致,而ssTnI启动子乙酰化水平在各组间差异无统计学意义(P>0.05),但E14.5组心脏中ERRα与ssTnI启动子结合水平显著高于其余各组(P<0.05),αMHC和βMHC启动子乙酰化水平在各组间比较差异无统计学意义(P>0.05),且ERRα与二者启动子结合水平亦在各组间比较差异无统计学意义(P>0.05)。结论ERRα作为转录因子直接调控心肌肌钙蛋白亚型转化,进而促进心肌细胞成熟。Objective To investigate the effect of estrogen-related receptorα(ERRα)on cardiomyocytes maturation.Methods Embryonic day of 14.5(E14.5),E17.5,new born(nb),postnatal 2-week(p2w)and postnatal 4-week(p4w)mice were used as experiment subjects.Heart samples were collected.Q-PCR and Western blot methods were used to detect mRNA and protein levels of ERRα,ssTnI,cTnI,αMHC andβMHC.ChIP assay were employed to determine the level of histone acetylation levels in the promoter regions of ssTnI,cTnI,αMHC andβMHC,and the binding levels of ERRαwith promoters of those genes.Results Expression levels of ERRα,cTnI andαMHC were increased gradually in heart development and maturation(P<0.05).Meanwhile,expression levels of ssTnI andβMHC were decreased(P<0.05).Acetylation levels in promoter region of cTnI was went up as the pattern of its gene expression(P<0.05).However,acetylation levels in promoter of ssTnI,αMHC andβMHC showed no significant changes among each group(P>0.05).Binding affinity of ERRαwith the promoter of cTnI was increased and reduced in promoter of ssTnI(P<0.05).Conclusion ERRαregulates TnI isoform switch to promote cardiomyocytes maturation.

关 键 词：心肌细胞成熟 雌激素受体Α 肌钙蛋白I 肌球蛋白重链蛋白 

分 类 号：R331.31[医药卫生—人体生理学]