Effects of regulator of G protein signaling 19 (RGS19) on heart development and function

Young Rae Ji, Myoung Ok Kim, Sung Hyun Kim, Dong Hun Yu, Mi Jung Shin, Hei Jung Kim, Hyung Soo Yuh, Ki Beom Bae, Jae Young Kim, Hum Dai Park, Sang Gyu Lee, Byung Hwa Hyun, Zae Young Ryoo

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Wnt/Wg genes play a critical role in the development of various organisms. For example, the Wnt/β-catenin signal promotes heart formation and cardiomyocyte differentiation in mice. Previous studies have shown that RGS19 (regulator of G protein signaling 19), which hasGα subunits with GTPase activity, inhibits the Wnt/β-catenin signal through inactivation of Gαo. In the present study, the effects of RGS19 on mouse cardiac development were observed. In P19 teratocarcinoma cells with RGS19 overexpression, RGS19 inhibited cardiomyocyte differentiation by blocking the Wnt signal. Additionally, several genes targeted by Wnt were down-regulated. For the in vivo study, we generated RGS19-overexpressing transgenic (RGS19 TG) mice. In these transgenic mice, septal defects and thin-walled ventricles were observed during the embryonic phase of development, and the expression of cardiogenesis-related genes, BMP4 and Mef2C, was reduced significantly. RGS19 TG mice showed increased expression levels of brain natriuretic peptide and β-MHC, which are markers of heart failure, increase of cell proliferation, and electrocardiogram analysis shows abnormal ventricle repolarization. These data provide in vitro and in vivo evidence that RGS19 influenced cardiac development and had negative effects on heart function.

Original languageEnglish (US)
Pages (from-to)28627-28634
Number of pages8
JournalJournal of Biological Chemistry
Volume285
Issue number37
DOIs
StatePublished - Sep 10 2010

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