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丁香酸通过下调 Ereg 减轻异丙肾上腺素诱导的心脏肥大和纤维化。

Syringic acid mitigates isoproterenol-induced cardiac hypertrophy and fibrosis by downregulating Ereg.

机构信息

Heart Research Center of Chonnam National University Hospital, Gwangju, Korea.

Hypertension Heart Failure Research Center, Chonnam National University Hospital, Gwangju, Korea.

出版信息

J Cell Mol Med. 2022 Jul;26(14):4076-4086. doi: 10.1111/jcmm.17449. Epub 2022 Jun 19.

Abstract

Gallic acid has been reported to mitigate cardiac hypertrophy, fibrosis and arterial hypertension. The effects of syringic acid, a derivative of gallic acid, on cardiac hypertrophy and fibrosis have not been previously investigated. This study aimed to examine the effects of syringic acid on isoproterenol-treated mice and cells. Syringic acid mitigated the isoproterenol-induced upregulation of heart weight to bodyweight ratio, pathological cardiac remodelling and fibrosis in mice. Picrosirius red staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses revealed that syringic acid markedly downregulated collagen accumulation and fibrosis-related factors, including Fn1. The results of RNA sequencing analysis of Ereg expression were verified using qRT-PCR. Syringic acid or transfection with si-Ereg mitigated the isoproterenol-induced upregulation of Ereg, Myc and Ngfr. Ereg knockdown mitigated the isoproterenol-induced upregulation of Nppb and Fn1 and enhancement of cell size. Mechanistically, syringic acid alleviated cardiac hypertrophy and fibrosis by downregulating Ereg. These results suggest that syringic acid is a potential therapeutic agent for cardiac hypertrophy and fibrosis.

摘要

没食子酸已被报道可减轻心肌肥厚、纤维化和动脉高血压。没食子酸的衍生物丁香酸对心肌肥厚和纤维化的影响尚未被研究过。本研究旨在探讨丁香酸对异丙肾上腺素处理的小鼠和细胞的影响。丁香酸减轻了异丙肾上腺素诱导的小鼠心脏重量与体重比、病理性心脏重构和纤维化的上调。天狼猩红染色、实时定量聚合酶链反应(qRT-PCR)和 Western blot 分析表明,丁香酸显著地下调了胶原积累和纤维化相关因子,包括 Fn1。Ereg 表达的 RNA 测序分析结果通过 qRT-PCR 得到验证。丁香酸或 si-Ereg 转染减轻了异丙肾上腺素诱导的 Ereg、Myc 和 Ngfr 的上调。Ereg 敲低减轻了异丙肾上腺素诱导的 Nppb 和 Fn1 的上调和细胞大小的增强。在机制上,丁香酸通过下调 Ereg 来减轻心肌肥厚和纤维化。这些结果表明,丁香酸是治疗心肌肥厚和纤维化的一种有潜力的治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b63/9279583/295abfe8634e/JCMM-26-4076-g003.jpg

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