gp130 plays a critical role in pressure overload-induced cardiac hypertrophy.
gp130, a common receptor for the interleukin 6 family, plays pivotal roles in growth and survival of cardiac myocytes. In the present study, we examined the role of gp130 in pressure overload-induced cardiac hypertrophy using transgenic (TG) mice, which express a dominant negative mutant of gp130 in the heart under the control of alpha myosin heavy chain promoter. TG mice were apparently healthy and fertile. There were no differences in body weight and heart weight between TG mice and littermate wild type (WT) mice. Pressure overload-induced increases in the heart weight/body weight ratio, ventricular wall thickness, and cross-sectional areas of cardiac myocytes were significantly smaller in TG mice than in WT mice. Northern blot analysis revealed that pressure overload-induced up-regulation of brain natriuretic factor gene and down-regulation of sarcoplasmic reticulum Ca(2+) ATPase 2 gene were attenuated in TG mice. Pressure overload activated ERKs and STAT3 in the heart of WT mice, whereas pressure overload-induced activation of STAT3, but not of ERKs, was suppressed in TG mice. These results suggest that gp130 plays a critical role in pressure overload-induced cardiac hypertrophy possibly through the STAT3 pathway.
Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan.
H
H
Uozumi
Y
Y
Hiroi
Y
Y
Zou
E
E
Takimoto
H
H
Toko
P
P
Niu
M
M
Shimoyama
Y
Y
Yazaki
R
R
Nagai
I
I
Komuro
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D001835:Body Weight; D006332:Cardiomegaly / Q000503:physiopathology*; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D020287:In Situ Nick-End Labeling; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009929:Organ Size; D011312:Pressure; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D004268:DNA-Binding Proteins; C494200:Il6st protein, mouse; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D020928:Mitogen-Activated Protein Kinases