AUTOINDUCTION OF MESSENGER-RNA AND PROTEIN EXPRESSION FOR TRANSFORMING GROWTH FACTOR-BETA-S IN CULTURED CARDIAC-CELLS

Although transforming growth factor-beta s (TGF-beta s) are expressed widely in both adult and embryonic rat heart, both mRNA and protein expression increase following ischemic injury, Furthermore, exogenous administration of TGF-beta 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-beta 1, 2, or 3 results in increased expression of TGF-beta 1, 2, and 3 mRNA, TGF-beta 2 was generally the least effective isoform in inducing TGF-beta expression. In cardiac fibroblasts mRNA expression of all TGF-beta s 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-beta 1 and 2 protein secretion, respectively By 48 h of treatment mRNA levels for TGF-beta s 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-beta 1 treatment, but TGF-beta 1 and 3 mRNA levels returned to control values by 48 h while TGF-beta 2 mRNA expression remained elevated, TGF-beta 1 and 2 protein secreted by the cardiac myocytes was increased 2.9- and 1.7-fold, respectively. Autoinduction of TGF-beta s may play a beneficial role in cardiac wound healing by sustaining transient increases in TGF-beta levels from either endogenous synthesis or exogenous application.