Autoinduction of mRNA 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.
Flanders
K C
KC
Laboratory of Chemoprevention, National Cancer Institute, Bethesda, MD 20892, USA.
Holder
M G
MG
Winokur
T S
TS
D000818:Animals; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism*; D006706:Homeostasis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D016212:Transforming Growth Factor beta / Q000096:biosynthesis* / Q000494:pharmacology
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta