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microRNA-133a 通过靶向 PKCδ 和 Gq 减轻心肌细胞肥大。

microRNA-133a attenuates cardiomyocyte hypertrophy by targeting PKCδ and Gq.

机构信息

Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Republic of Korea.

Department of Integrated Omics for Biomedical Sciences, Yonsei University, Seoul, Republic of Korea.

出版信息

Mol Cell Biochem. 2018 Feb;439(1-2):105-115. doi: 10.1007/s11010-017-3140-8. Epub 2017 Aug 9.

Abstract

During the past decade, microRNAs have continuously been suggested as a promising therapeutic tool due to their beneficial effects, such as their multi-targets and multi-functions in pathologic conditions. As a pathologic phenotype is generally regulated by multiple signaling pathways, in this study we identified a microRNA regulating multiple target genes within cardiac hypertrophic signaling pathways. microRNA-133a is known to play a crucial role in cardiac hypertrophy. However, the role of microRNA-133a, which may regulate several signaling pathways in norepinephrine-induced cardiac hypertrophy via multi-targeting, has not been investigated. In the current study, we showed that microRNA-133a can protect cardiomyocyte hypertrophy against norepinephrine stimulation in neonatal rat ventricular cardiomyocytes via new targets, PKCδ and Gq, all of which are related to downstream signaling pathways of the α-adrenergic receptor. Taken together, these results suggest the advantages of the therapeutic use of microRNAs as an effective potential drug regulating multiple signaling pathways under pathologic conditions.

摘要

在过去的十年中,由于 microRNAs 在病理条件下具有多靶点和多功能等有益作用,它们不断被认为是一种有前途的治疗工具。由于病理表型通常受多种信号通路调节,在本研究中,我们鉴定了一种调节心脏肥厚信号通路中多个靶基因的 microRNA。miR-133a 已知在心脏肥厚中起关键作用。然而,miR-133a 的作用可能通过多靶向调节去甲肾上腺素诱导的心脏肥厚中的几个信号通路,尚未得到研究。在本研究中,我们表明,microRNA-133a 可以通过新的靶标 PKCδ 和 Gq 保护心肌细胞肥大对抗去甲肾上腺素刺激,所有这些靶标都与 α-肾上腺素能受体的下游信号通路有关。综上所述,这些结果表明,microRNAs 作为一种有效的潜在药物,在病理条件下调节多个信号通路的治疗用途具有优势。

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