Coordinate TGF-beta receptor gene expression during rat heart development.

Abstract

Transforming growth factor-beta (TGF-beta) has been implicated to participate in heart development. The receptors which transduce the signal(s) mediated by TGF-beta ligand binding have only recently been cloned. One of the most prominent effects of TGF-beta is inhibition of cell proliferation, a process that is tightly regulated during heart development. Using the developing rat ventricle as a model system, we have determined the steady state expression patterns for the Type I, II, and III TGF-beta receptors (TGF-beta Rs). Using RNA isolated from ventricular chambers on day 18 of gestation through the ninth postnatal week of age, we detected a modest increase in expression levels for Type I and Type III TGF-beta Rs. In contrast, steady state transcript levels for the Type II TGF-beta R showed a profound developmental increase from nearly undetectable levels at the fetal ages examined to high levels during the first postnatal week of age. Immunoelectron microscopic localization of Type II TGF-beta R confirmed that the 3-week-old ventricular myocyte, as well as nonmyocytes, contained immunoreactive material. Immunoreactivity was found at both the cell surface as well as intracellular compartment. Regional variations (right ventricle, left ventricle, or septum) in the expression pattern of several markers of heart development, but not the TGF-beta R's, were found in RNA obtained from 3-week-old postnatal animals. These data suggest that "downstream" effectors of TGF-beta-mediated stimulation are modulated in a developmental, regional-specific manner in the neonatal/mature myocardium by the level of bioactive TGF-beta.