Regulator of G Protein Signaling 3 Protects Against Cardiac Hypertrophy in Mice
Regulator of G Protein Signaling 3 Protects Against Cardiac Hypertrophy in Mice
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G 蛋白信号传导 3 的调节剂可预防小鼠心脏肥大。
DOI：
10.1002/jcb.24741
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发表时间：
2014-05-01
影响因子：
4
通讯作者：
Huang, Congxin
中科院分区：
文献类型：
--
作者：
Liu, Yu;Huang, He;Huang, Congxin
G 蛋白信号传导调节因子 3 (RGS3) 是 G 蛋白介导的信号传导的负调节因子。 RGS3 先前已被证明在成熟心脏内的各种细胞类型中表达。基础和临床研究报告了肥厚心脏和衰竭心肌中 RGS3 的异常表达。然而，RGS3 在心脏重塑中的作用仍不清楚。在这项研究中，我们研究了人 RGS3 心脏过表达对 RGS3 转基因小鼠和野生型同窝小鼠主动脉束带 (AB) 诱导的心脏肥大的影响。通过超声心动图以及心脏样本的病理学和分子分析来评估心脏肥大的程度。心脏中 RGS3 的过度表达显着降低了 AB 引起的心脏肥大、纤维化和左心室功能障碍的程度。这些有益作用与 MEK-ERK1/2 信号传导的抑制有关。在培养的新生大鼠心肌细胞中进行的体外研究证实，RGS3 过度表达可抑制血管紧张素 II 诱导的肥大性生长，这与 MEK-ERK1/2 信号传导的减弱有关。因此，RGS3 的心脏过度表达可抑制适应不良肥厚和纤维化，并通过阻断 MEK-ERK1/2 信号传导来改善心脏功能。 J.细胞。生物化学。 115：977-986，2014 年。(c) 2013 年 Wiley 期刊公司。
Regulator of G protein signaling 3 (RGS3) is a negative regulator of G protein-mediated signaling. RGS3 has previously been shown to be expressed among various cell types within the mature heart. Basic and clinical studies have reported abnormal expressions of RGS3 in hypertrophic hearts and in the failing myocardium. However, the role of RGS3 in cardiac remodeling remains unclear. In this study, we investigated the effect of cardiac overexpression of human RGS3 on cardiac hypertrophy induced by aortic banding (AB) in RGS3 transgenic mice and wild-type littermates. The extent of cardiac hypertrophy was evaluated by echocardiography as well as pathological and molecular analyses of heart samples. RGS3 overexpression in the heart markedly reduced the extent of cardiac hypertrophy, fibrosis, and left ventricular dysfunction in response to AB. These beneficial effects were associated with the inhibition of MEK-ERK1/2 signaling. In vitro studies performed in cultured neonatal rat cardiomyocytes confirmed that RGS3 overexpression inhibits hypertrophic growth induced by angiotensin II, which was associated with the attenuation of MEK-ERK1/2 signaling. Therefore, cardiac overexpression of RGS3 inhibits maladaptive hypertrophy and fibrosis and improves cardiac function by blocking MEK-ERK1/2 signaling. J. Cell. Biochem. 115: 977-986, 2014. (c) 2013 Wiley Periodicals, Inc.