HERC2通过激活PI3K-AKT信号促进心肌细胞肥大  

HERC2 promotes cardiomyocyte hypertrophy via activating PI3K-AKT pathway

作　　者：高伟年[1] 赵曙光[1] 郭娜[2] 陈子英[1] 张文立[1] 于丁[1] GAO Wei-nian;ZHAO Shu-guang;GUO Na;CHEN Zi-ying;ZHANG Wen-li;YU Ding(Department of Cardiac Macrovascular Surgery, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China;First Department of Cardiology, Shijiazhuang Traditional Chinese Medicine Hospital, Hebei Province, Shijiazhuang 050051, China)

机构地区：[1]河北医科大学第二医院心脏大血管外科,河北石家庄050000 [2]河北省石家庄市中医院心病一科,河北石家庄050051

出　　处：《河北医科大学学报》2020年第6期632-636,共5页Journal of Hebei Medical University

基　　金：河北省医学科学研究课题计划(20190058)。

摘　　要：目的探讨HECT和RLD结构域的E3连接酶2(HECT and RLD domain containing E3 ubiquitin protein ligase 2,HERC2)在心肌肥厚中的功能与机制。方法选取心肌肥厚患者和对照组心肌组织,实时荧光定量逆转录聚合酶链反应(quantitative reverse transcription-polymerase chain reaction,qRT-PCR)分析心肌肥厚标志基因及HERC2基因表达水平。在SD大鼠中用血管紧张素Ⅱ诱导心肌肥厚,qRT-PCR分析心肌组织中心肌肥厚标志基因与HERC2基因表达水平。取SD乳鼠心肌细胞,siRNA干扰HERC2表达后用血管紧张素Ⅱ诱导心肌细胞肥大,分析心肌细胞大小及心肌肥厚标志基因表达水平,Western blot分析磷脂肌醇-3激酶/AKT丝氨酸-苏氨酸激酶(phosphatidylinositol 3-kinase/AKT serine/threonine kinase,PI3K-AKT)信号活化水平。结果与对照组相比,心肌肥厚患者心肌组织中HERC2表达水平明显增加。在血管紧张素Ⅱ诱导的心肌肥厚大鼠心肌组织中,HERC2基因表达水平同样显著增加。在大鼠心肌细胞中干扰HERC2表达可以抑制血管紧张素Ⅱ诱导的心肌细胞面积增大,抑制心肌肥厚相关标志基因心房利钠肽、脑钠肽和肌球蛋白重链7的表达。结论HERC2在心肌肥厚过程中高表达,HERC2可以通过调控PI3K-AKT信号通路促进心肌细胞肥大。Objective To investigate the roles and mechanism of HECT and RLD domain containing E3 ubiquitin protein ligase 2(HERC2)in cardiac hypertrophy.Methods The expression of hypertrophic genes and HERC2 were analyzed in the myocardial tissues from patients with hypertrophic cardiomyopathy and the controls by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).Cardiac hypertrophy was induced in rat with angiotensinⅡ,and the expression of hypertrophic genes and HERC2 was analyzed.siRNA was used to knock down HERC2 in cardiomyocytes and cardiomyocyte hypertrophy was induced with angiotensinⅡ.Then,the cardiomyocyte size,expression of hypertrophic genes and activation of the phosphatidylinositol 3-kinase/AKT serine/threonine kinase(PI3K-AKT)signaling were analyzed.Results The expressions of HERC2 were significantly upregulated in the myocardial tissues of patients with hypertrophic cardiomyopathy compared with the controls.The overexpression of HERC2 was also observed in rat cardiac hypertrophy induced by angiotensinⅡ.Knockdown of HERC2 with siRNA repressed angiotensinⅡ-induced increase in cardiomyocyte size and expression of hypertrophic genes natriuretic peptide A,natriuretic peptide B and myosin heavy chain 7.Conclusion HERC2 is highly expressed in the process of cardiac hypertrophy.HERC2 can promote cardiac hypertrophy by regulating PI3K-Akt signaling pathway.

关 键 词：心肌病 肥厚性 血管紧张素Ⅱ 磷酸肌醇3-激酶 

分 类 号：R542.2[医药卫生—心血管疾病]