Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity.
Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity.
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DOI：
10.1038/srep34790
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发表时间：
2016-10-05
影响因子：
4.6
通讯作者：
Jeong MH
中科院分区：
文献类型：
--
作者：
Ryu Y;Jin L;Kee HJ;Piao ZH;Cho JY;Kim GR;Choi SY;Lin MQ;Jeong MH
没食子酸是一种酚酸，已被证明对炎症、血管钙化和代谢疾病具有有益作用。本研究旨在探讨没食子酸对心肌肥厚和纤维化的影响及其调控机制。用异丙肾上腺素（ISP）诱导小鼠和原代乳鼠心肌细胞肥大。没食子酸预处理减轻向心性心肌肥厚。它在体内和体外下调心钠素、脑钠素和β-肌球蛋白重链的表达。此外，它还阻止了间质胶原沉积和纤维化相关基因的表达。在心肌成肌细胞H9 c2细胞中观察到Smad 3过表达上调I型胶原，但在心脏成纤维细胞中未观察到。没食子酸降低大鼠心肌成纤维细胞I型胶原启动子Smad结合位点磷酸化Smad 3的DNA结合活性。此外，它还能降低ISP诱导的小鼠c-Jun N-末端激酶（JNK）和细胞外信号调节激酶（ERK）蛋白的磷酸化。JNK 2过表达降低了H9 c2细胞和心脏成纤维细胞中I型胶原和Smad 3的表达以及GATA 4的表达。没食子酸可能通过调控JNK 2和Smad 3信号通路而成为预防心肌肥厚和纤维化的新的治疗药物。
Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway.
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DOI：
10.1186/1755-1536-5-15
发表时间：
2012-09-03
期刊：
Fibrogenesis & tissue repair
影响因子：
--
作者：
Fan D;Takawale A;Lee J;Kassiri Z
通讯作者：
Kassiri Z
影响因子：
37.8
作者：
Kehat I;Molkentin JD
通讯作者：
Molkentin JD
DOI：
10.1152/ajpheart.00514.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Banerjee, Indroneal;Fuseler, John W.;Baudino, Troy A.
通讯作者：
Baudino, Troy A.
影响因子：
10.8
作者：
Hsu, Steven;Nagayama, Takahiro;Takimoto, Eiki
通讯作者：
Takimoto, Eiki
影响因子：
8.3
作者：
Huang, Xiao R.;Chung, Arthur C. K.;Lan, Hui Y.
通讯作者：
Lan, Hui Y.