TRANSFORMING GROWTH-FACTOR-BETA IN CARDIAC ONTOGENY AND ADAPTATION

The transforming growth factor-beta (TGF-beta) superfamily comprises a set of regulatory peptides with multiple effects on cell growth and differentiation. The elaborate regulation of TGF-betas during embryonic development of the heart, the upregulation of TGF-beta after hemodynamic stress, and the impact of TGF-beta on cardiac gene expression together imply a prominent functional role for this family of growth factors in cardiac organogenesis and hypertrophy. Basal and TGF-beta-induced expression of skeletal alpha-actin, one of several genes specifically associated with developing or hypertrophied myocardium, each are contingent on transcriptional activation by serum response factor. A truncated form of the type II TGF-beta receptor, created by deletion of the cytoplasmic kinase domain, acts as a dominant suppressor of TGF-beta signal transduction in cultured cardiac muscle cells and may provide a suitable means to establish the functions of TGF-beta in vivo.