Autoinduction of mRNA and protein expression for transforming growth factor-βs in cultured cardiac cells

Abstract

K. C. Flanders, M. G. Holder and T. S. Winokur. Autoinduction of mRNA and Protein Expression for Transforming Growth Factor-βs in Cultured Cardiac Cells. Journal of Molecular and Cellular Cardiology (1995) 27, 805–812. Although transforming growth factor-βs (TGF-βs) are expressed widely in both adult and embryonic rat heart, both mRNA and protein expression increase following ischemic injury. Furthermore, exogenous administration of TGF-β decreases cardiac damage following ischemia-reperfusion in rats. We have found that treatment of primary cultures of neonatal rat cardiomyocytes or cardiac fibroblasts with TGF-β 1, 2, or 3 results in increased expression of TGF-β 1, 2, and 3 mRNA. TGF-β2 was generally the least effective isoform in inducing TGF-β expression. In cardiac fibroblasts mRNA expression of all TGF-βs increased 2–3-fold following 1 h of treatment and decreased to control levels by 8 h which was accompanied by a 2.5− and 2.3-fold increase in TGF-β 1 and 2 protein secretion, respectively. By 48 h of treatment mRNA levels for TGF-βs 2 and 3 were less than 10% of control levels. In cardiomyocytes two-five-fold increases in mRNA levels were observed following 1–24 h of TGF-β1 treatment, but TGF-β1 and 3 mRNA levels returned to control values by 48 h while TGF-β2 mRNA expression remained elevated. TGF-β 1 and 2 protein secreted by the cardiac myocytes was increased 2.9− and 1.7-fold, respectively. Autoinduction of TGF-βs may play a beneficial role in cardiac wound healing by sustaining transient increases in TGF-β levels from either endogenous synthesis or exogenous application.