Cardiomyocyte-Specific T beta R2 Knockout Mice are More Susceptible to Cardiac Hypertrophy Induced by Adrenergic Agonist Stimulation

TGF-beta 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-beta type 2 receptor (T beta R2) knockout mice to study the function of TGF-beta signaling in cardiac hypertrophy. Although the mutant mice displayed no obvious physiological abnormality, they developed severe 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 T beta R2 knockout mice, while inhibition of MEK-1-mediated activation of MAPK using PD98059 partially rescued the phenotype of T beta R2-deleted cardiomyocytes, indicating that activation of TGF-beta noncanonical signaling might contribute to cardiac phenotype observed in T beta R2 knockout mice. Thus, our data provided the first in vivo genetic evidence to show that T beta R2 may function as an anti-hypertrophic factor of cardiac hypertrophy subjected to adrenergic stimulation, suggesting the complex role of T beta R2 in cardiac hypertrophy under stimulation of different stresses.