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学科主题临床医学
Enhanced MiR-711 transcription by PPAR gamma induces endoplasmic reticulum stress-mediated apoptosis targeting calnexin in rat cardiomyocytes after myocardial infarction
Zhao, Na1; Mi, Lan3; Zhang, Xunjun1; Xu, Minyao4; Yu, Haiyi2; Liu, Zhongwei1; Liu, Xiaojun1; Guan, Gongchang1; Gao, Wei2; Wang, Junkui1
通讯作者Gao, Wei(2) ; Wang, Junkui(1)
刊名JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
2018-05-01
DOI10.1016/j.yjmcc.2018.03.006
118页:36-45
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Cell Biology
研究领域[WOS]Cardiovascular System & Cardiology ; Cell Biology
关键词[WOS]UNFOLDED PROTEIN RESPONSE ; ER STRESS ; GENES ; MICRORNAS ; ACTIVATION ; CASPASE-12 ; PATHWAY ; LONG
英文摘要

MicroRNA 711 (miR-711) levels in the heart change dynamically after myocardial infarction (MI). As peroxisome proliferator-activated receptor gamma (PPAR gamma) can upregulate miR-711 in adipocytes and cardiac fibroblasts, this study examined the precise mechanism of PPAR gamma-mediated miR-711 upregulation and its role in the heart in the early stages after MI. In a rat model of MI induced by left anterior descending coronary artery ligation, immunohistochemical and western blot analyses revealed increased PPAR gamma expression in cardiomyocyte nuclei after MI. PPAR gamma modulated miR-711 levels in neonatal rat cardiomyocytes, and chromatin immunoprecipitation and luciferase assays revealed that it bound the premiR-711 promoter to upregulate miR-711. Bioinformatics analysis identified calnexin as a putative miR-711 target; this was confirmed by luciferase, western blot, and real-time polymerase chain reaction analyses. Additionally, the transfection of a miR-711 mimic into cardiomyocytes induced the endoplasmic reticulum (ER) stress -induced apoptosis response by up regulating glucose-regulated protein 78 (GRP78), activating transcription factor (ATF6), spliced X-box binding protein 1 (XBP1), apoptotic signal-regulating kinase 1 (ASK1), CCAAT-enhancer binding protein homologous protein (CHOP), caspase-12, and endoplasmic reticulum oxidoreductase 1 alpha (ERO1a). Similarly, on day 2 after MI, increased miR-711 levels in the heart were accompanied by increased cardiomyocyte apoptosis, decreased calnexin levels, and increased levels of GRP78, ATF6, spliced XBP1, ASK1, CHOP, and caspase-12, as well as cardiomyocytes apoptosis. The mechanism underlying these effects may involve the direct binding of PPARy to the pre-miR-711 promoter for the upregulation of miR-711, which may induce ER stress-mediated cardiomyocyte apoptosis via calnexin. These findings augment the general knowledge of the post-MI pathological process and suggest a therapeutic strategy for cardiac remodelling in the early stages after MI.

语种英语
WOS记录号WOS:000432499700004
通讯作者邮箱weigao@bjmu.edu.cn ; 17792019987@163.com
第一作者单位Shaanxi Prov Peoples Hosp, Dept Cardiovasc Med, Xian, Shaanxi, Peoples R China
通讯作者单位Shaanxi Prov Peoples Hosp, Dept Cardiovasc Med, Xian, Shaanxi, Peoples R China ; Peking Univ, Hosp 3, Minist Hlth,Key Lab Mol Cardiovasc Sci,Minist Edu, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing, Peoples R China
ISSN0022-2828
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/141878
专题北京大学第三临床医学院_心血管内科
作者单位1.Shaanxi Prov Peoples Hosp, Dept Cardiovasc Med, Xian, Shaanxi, Peoples R China;
2.Peking Univ, Hosp 3, Minist Hlth,Key Lab Mol Cardiovasc Sci,Minist Edu, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing, Peoples R China;
3.Peking Univ Canc Hosp & Inst, Minist Educ, Key Lab Carcinogenesis & Translat Res, Dept Med Affairs, Beijing, Peoples R China;
4.ZTE Corp, Xian, Shaanxi, Peoples R China
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GB/T 7714
Zhao, Na,Mi, Lan,Zhang, Xunjun,et al. Enhanced MiR-711 transcription by PPAR gamma induces endoplasmic reticulum stress-mediated apoptosis targeting calnexin in rat cardiomyocytes after myocardial infarction[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2018,118:36-45.
APA Zhao, Na.,Mi, Lan.,Zhang, Xunjun.,Xu, Minyao.,Yu, Haiyi.,...&Wang, Junkui.(2018).Enhanced MiR-711 transcription by PPAR gamma induces endoplasmic reticulum stress-mediated apoptosis targeting calnexin in rat cardiomyocytes after myocardial infarction.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,118,36-45.
MLA Zhao, Na,et al."Enhanced MiR-711 transcription by PPAR gamma induces endoplasmic reticulum stress-mediated apoptosis targeting calnexin in rat cardiomyocytes after myocardial infarction".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 118(2018):36-45.
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