Peptide growth factors can provoke "fetal" contractile protein gene expression in rat cardiac myocytes.
Cardiac-specific gene expression is intricately regulated in response to developmental, hormonal, and hemodynamic stimuli. To test whether cardiac muscle might be a target for regulation by peptide growth factors, the effect of three growth factors on the actin and myosin gene families was investigated by Northern blot analysis in cultured neonatal rat cardiac myocytes. Transforming growth factor-beta 1 (TGF beta 1, 1 ng/ml) and basic fibroblast growth factor (FGF, 25 ng/ml) elicited changes corresponding to those induced by hemodynamic load. The "fetal" beta-myosin heavy chain (MHC) was up-regulated about four-fold, whereas the "adult" alpha MHC was inhibited greater than 50-60%; expression of alpha-skeletal actin increased approximately two-fold, with little or no change in alpha-cardiac actin. Thus, peptide growth factors alter the program of differentiated gene expression in cardiac myocytes, and are sufficient to provoke fetal contractile protein gene expression, characteristic of pressure-overload hypertrophy. Acidic FGF (25 ng/ml) produced seven- to eightfold reciprocal changes in MHC expression but, unlike either TGF-beta 1 or basic FGF, inhibited both striated alpha-actin genes by 70-90%. Expression of vascular smooth muscle alpha-actin, the earliest alpha-actin induced during cardiac myogenesis, was increased by all three growth factors. Thus, three alpha-actin genes demonstrate distinct responses to acidic vs. basic FGF.
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
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D000199:Actins / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008285:Major Histocompatibility Complex; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000235:genetics*; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D015291:Transforming Growth Factors / Q000494:pharmacology*
D000199:Actins; D005346:Fibroblast Growth Factors; D012313:RNA; D015291:Transforming Growth Factors; D009218:Myosins