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MiR-130a inhibition protects rat cardiac myocytes from hypoxia-triggered apoptosis by targeting Smad4

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成果类型:
期刊论文
作者:
Li, Yuanshi;Du, Yingrong;Cao, Junxian;Gao, Qianping;Li, Hongjuan;Chen, Yangjun;Lu, Nihong
通讯作者:
Lu, NH
作者机构:
[Cao, Junxian; Gao, Qianping; Li, Yuanshi] Harbin Med Univ, Affiliated Hosp 1, Cardiovasc Dept, Harbin, Heilongjiang, Peoples R China.
[Li, Hongjuan; Du, Yingrong] Third Peoples Hosp Kunming, Dept Cardiovasc Med, Kunming, Yunnan, Peoples R China.
[Lu, Nihong; Chen, Yangjun] Third Peoples Hosp Kunming, Dept Resp Med, Kunming, Yunnan, Peoples R China.
通讯机构:
[Lu, NH] Third Peoples Hosp 319 Kunming, Dept Resp Med, Kunming 650000, Yunnan, Peoples R China.
语种:
英文
关键词:
apoptosis;cardiomyocyte;hypoxia;miR-130a;Smad4
期刊:
KARDIOLOGIA POLSKA
ISSN:
0022-9032
年:
2018
卷:
76
期:
6
页码:
993-1001
文献类别:
WOS:Article
所属学科:
WOS学科类别:Cardiac & Cardiovascular Systems
入藏号:
基金类别:
Key Project of Kunming Science and Technology Bureau [2015-2-S-01378]
机构署名:
本校为其他机构
院系归属:
第一临床医学院
摘要:
Background: Cardiomyocyte death facilitates the pathological process underlying ischaemic heart diseases, such as myocardial infarction. Emerging evidence suggests that microRNAs play a critical role in the pathological process underlying myocardial infarction by regulating cardiomyocyte apoptosis. However, the relevance of miR-130a in regulating cardiomyocyte apoptosis and the underlying mechanism are still uncertain. Aim: We sought to explore the regulatory effect of miR-130a on hypoxic cardiomyocyte apoptosis. Methods: The expression of miR-130a was measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell survival was determined by the MTT assay. The lactate dehydrogenase (LDH) assay was performed to determine the severity of hypoxia-induced cell injury. Apoptosis was assessed via caspase-3 analysis. Protein expression level was determined by Western blotting. The genes targeted by miR-130a were predicted using bioinformatics and were validated via the dual-luciferase reporter assay system. Results: We found that miR-130a expression was greatly increased in hypoxic cardiac myocytes, and that the downregulation of miR-130a effectively shielded cardiac myocytes from hypoxia-triggered apoptosis. In bioinformatic analysis the Smad4 gene was predicted to be the target of miR-130a. This finding was validated through the Western blot assay, dual-luciferase reporter gene assay, and qRT-PCR. MiR-130a inhibition significantly promoted the activation of Smad4 in hypoxic cardiomyocytes. Interestingly, knockdown of Smad4 markedly reversed the protective effects induced by miR-130a inhibition. Moreover, we found that the inhibition of miR-130a promoted the activation of transforming growth factor-beta 1 signalling. Blocking of Smad4 signalling significantly abrogated the protective effects of miR-130a inhibition. Conclusions: The findings indicate that inhibition of miR-130a, which targets the Smad4 gene, shields cardiac myocytes from hypoxic apoptosis. This study offers a novel perspective on the molecular basis of hypoxia-induced cardiomyocyte apoptosis and suggests a possible drug target for the treatment of myocardial infarction.
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