Transforming growth factor-β in cardiac ontogeny and adaptation

Abstract

The transforming growth factor-β (TGF-β) superfamily comprises a set of regulatory peptides with multiple effects on cell growth and differentiation. The elaborate regulation of TGF-βs during embryonic development of the heart, the upregulation of TGF-β after hemodynamic stress, and the impact of TGF-β on cardiac gene expression together imply a prominent functional role for this family of growth factors in cardiac organogenesis and hypertrophy. Basal and TGF-β-induced expression of skeletal α-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-β receptor, created by deletion of the cytoplasmic kinase domain, acts as a dominant suppressor of TGF-β signal transduction in cultured cardiac muscle cells and may provide a suitable means to establish the functions of TGF-β in vivo.