TY - JOUR
T1 - Antihypertrophic effects of adiponectin on cardiomyocytes are associated with the inhibition of heparin-binding epidermal growth factor signaling
AU - Liao, Yulin
AU - Xuan, Wanling
AU - Zhao, Jing
AU - Bin, Jianpin
AU - Zhao, Hui
AU - Asakura, Masanori
AU - Funahashi, Tohru
AU - Takashima, Seiji
AU - Kitakaze, Masafumi
PY - 2010/3/12
Y1 - 2010/3/12
N2 - This study was aimed to investigate whether the antihypertrophic effects of adiponectin in murine hearts are associated with the modulation of HB-EGF signaling. We determined the myocardial expressions of adiponectin and adiponectin receptors, brain natriuretic peptide (BNP), and HB-EGF in normal and hypertrophied hearts of adiponectin knockout mice or wild-type mice with transverse aortic constriction (TAC). Then, we observed the effects of adiponectin on cardiac hypertrophy and HB-EGF signaling in cultured neonatal rat cardiomyocytes and whole hearts of adiponectin-null mice. The myocardial mRNA and protein expressions of adiponectin in the hypertrophied hearts were significantly downregulated, and the mRNA expression of adiponectin was inversely correlated with the heart-to-body weight ratio, BNP, and HB-EGF. The TAC-induced cardiac hypertrophy and EGF receptor (EGFR) activation in the adiponectin knockout mice were significantly greater than those in the wild-type mice. Furthermore, in vitro experiments revealed that adiponectin inhibited HB-EGF-stimulated protein synthesis, HB-EGF shedding, and EGFR phosphorylation. We conclude that the inhibition of HB-EGF mediated EGFR activation is one of the alternative mechanisms for the antihypertrophic action of adiponectin.
AB - This study was aimed to investigate whether the antihypertrophic effects of adiponectin in murine hearts are associated with the modulation of HB-EGF signaling. We determined the myocardial expressions of adiponectin and adiponectin receptors, brain natriuretic peptide (BNP), and HB-EGF in normal and hypertrophied hearts of adiponectin knockout mice or wild-type mice with transverse aortic constriction (TAC). Then, we observed the effects of adiponectin on cardiac hypertrophy and HB-EGF signaling in cultured neonatal rat cardiomyocytes and whole hearts of adiponectin-null mice. The myocardial mRNA and protein expressions of adiponectin in the hypertrophied hearts were significantly downregulated, and the mRNA expression of adiponectin was inversely correlated with the heart-to-body weight ratio, BNP, and HB-EGF. The TAC-induced cardiac hypertrophy and EGF receptor (EGFR) activation in the adiponectin knockout mice were significantly greater than those in the wild-type mice. Furthermore, in vitro experiments revealed that adiponectin inhibited HB-EGF-stimulated protein synthesis, HB-EGF shedding, and EGFR phosphorylation. We conclude that the inhibition of HB-EGF mediated EGFR activation is one of the alternative mechanisms for the antihypertrophic action of adiponectin.
KW - Adiponectin
KW - Heparin-binding epidermal growth factor
KW - Mouse
KW - Myocardial hypertrophy
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U2 - 10.1016/j.bbrc.2010.02.039
DO - 10.1016/j.bbrc.2010.02.039
M3 - Article
C2 - 20152812
AN - SCOPUS:77949261582
SN - 0006-291X
VL - 393
SP - 519
EP - 525
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -