Effects of regulator of G protein signaling 19 (RGS19) on heart development and function.
Wnt/Wg genes play a critical role in the development of various organisms. For example, the Wnt/beta-catenin signal promotes heart formation and cardiomyocyte differentiation in mice. Previous studies have shown that RGS19 (regulator of G protein signaling 19), which has Galpha subunits with GTPase activity, inhibits the Wnt/beta-catenin signal through inactivation of Galpha(o). 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 beta-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.
Ji
Young Rae
YR
School of Life Science and Biotechnology, Kyungpook National University, 1370 Sankyuk-dong, Buk-ku, Daegu 702-701, Korea.
Kim
Myoung Ok
MO
Kim
Sung Hyun
SH
Yu
Dong Hun
DH
Shin
Mi Jung
MJ
Kim
Hei Jung
HJ
Yuh
Hyung Soo
HS
Bae
Ki Beom
KB
Kim
Jae Young
JY
Park
Hum Dai
HD
Lee
Sang Gyu
SG
Hyun
Byung Hwa
BH
Ryoo
Zae Young
ZY
D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000196:embryology*; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D006343:Heart Septal Defects / Q000235:genetics / Q000378:metabolism; D064326:MEF2 Transcription Factors; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism
C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D044385:GTP-Binding Protein alpha Subunits; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; C551613:Myh7 protein, mouse; D018006:Myogenic Regulatory Factors; D020710:RGS Proteins; D051153:Wnt Proteins; C097187:regulator of G-protein signalling 19; D020097:Natriuretic Peptide, Brain; D018995:Myosin Heavy Chains