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Cardiomyocyte-Specific TβR2 Knockout Mice are More Susceptible to Cardiac Hypertrophy Induced by Adrenergic Agonist Stimulation

[ Vol. 16 , Issue. 5 ]

Author(s):

X. Fan, L. Liu, Z. Li, X. Peng, Z. Jiang, Y. Guan, X. Wu, X. Yang and J. Wang   Pages 496 - 503 ( 8 )

Abstract:


TGF-β signaling is shown to be involved in cardiac remodeling, but the detailed function and underlying mechanism are still incompletely understood. In this study, we generated cardiomyocyte-specific TGF-β type 2 receptor (TβR2) knockout mice to study the function of TGF-β signaling in cardiac hypertrophy. Although the mutant mice displayed no obvious physiological abnormality, they developed severer cardiac hypertrophy in response to isoproterenol (ISO) stimulation than control mice did. The expression of p-Smad2 was markedly reduced, while the concentration of p-ERK was increased in the hearts of mutant mice. In addition, we also found that cardiomyocyte-specific Smad2 knockout mice did not demonstrate cardiac phenotype as observed on TβR2 knockout mice, while inhibition of MEK-1-mediated activation of MAPK using PD98059 partially rescued the phenotype of TβR2-deleted cardiomyocytes, indicating that activation of TGF-β noncanonical signaling might contribute to cardiac phenotype observed in TβR2 knockout mice. Thus, our data provided the first in vivo genetic evidence to show that TβR2 may function as an anti-hypertrophic factor of cardiac hypertrophy subjected to adrenergic stimulation, suggesting the complex role of TβR2 in cardiac hypertrophy under stimulation of different stresses.

Keywords:

TβR2, conditional knockout mice, cardiac hypertrophy, ISO, Smad2, ERK

Affiliation:

The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, 410081, China., State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing 100071, China.



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