Regulation of mRNA transcripts and DNA synthesis in the rat heart following intravenous injection of transforming growth factor beta 1.
Transforming Growth Factor-beta 1 (TGF-beta 1) is expressed in the heart by muscle and non-muscle cardiac cells. In vitro, cardiac myocytes and non-muscle cells including cardiac fibroblasts and endothelial cells respond to regulatory effects of TGF-beta 1. Expression of TGF-beta 1 in the heart is subject to regulation by hemodynamic stimuli. Increased expression of mRNA transcripts for TGF-beta 1 has been reported in several models of cardiac hypertrophy. The objective of this study was to determine the effect of TGF-beta 1 in the myocardium. TGF-beta 1 was injected intravenously. Expression of mRNA transcripts for functional and structural proteins was determined by Northern hybridization analysis. DNA synthesis was determined by measurement of 3H-thymidine incorporation into ventricular DNA. The results showed differential regulation of mRNAs for myocyte- and non-myocyte-specific proteins in the heart of TGF-beta 1 treated rats. Moderate but statistically significant decrease in DNA synthesis was observed in the heart of TGF-beta 1 treated rats (37.5%, P < 0.025). Together, these data point to a physiological role for TGF-beta 1 in the heart. They further suggest that similar to its diverse in vitro cell-specific regulatory effects, TGF-beta 1 may have multicellular targets in the heart. Effect of TGF-beta 1 alone or combined with those of other cytokines/hormones that come into play, as the result of its administration, may be responsible for altered gene expression and DNA synthesis in the myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Sigel
A
A
Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06510.
Douglas
J A
JA
Eghbali-Webb
M
M
D000818:Animals; D001835:Body Weight; D004247:DNA / Q000096:biosynthesis*; D015870:Gene Expression; D006352:Heart Ventricles; D007275:Injections, Intravenous; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000502:physiology*
D009124:Muscle Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004247:DNA