Peptide growth factors can provoke "fetal" contractile protein gene expression in rat cardiac myocytes.

Abstract

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-ftI (TGFfl1, 1 ng/ml) and basic fibroblast growth factor (FGF, 25 ng/ml) elicited changes corresponding to those induced by hemodynamic load. The "fetal" ,B-myosin heavy chain (MHC) was up-regulated about fourfold, whereas the "adult" aMHC was inhibited > 50-60%; expression of a-skeletal actin increased approximately twofold, with little or no change in a-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 pressureoverload hypertrophy. Acidic FGF (25 ng/ml) produced sevento eightfold reciprocal changes in MHC expression but, unlike either TGF-fil or basic FGF, inhibited both striated a-actin genes by 70-90%. Expression of vascular smooth muscle aactin, the earliest a-actin induced during cardiac myogenesis, was increased by all three growth factors. Thus, three a-actin genes demonstrate distinct responses to acidic vs. basic FGF. (J. Clin. Invest. 1990. 85:507-514.) actin -myosin * fibroblast growth factor * transforming growth factor-#1l -cardiac hypertrophy

E2F-1 Regulates the Expression of a Subset of Target Genes during Skeletal Myoblast Hypertrophy

“…The hypertrophic response is initiated by a range of stimuli such as growth factors, hormones, cytokines, vasoactive peptides, and catecholamines (53)(54)(55)(56)(57)(58), and while the intracellular pathways that are activated may distinguish pathologic from physiologic cell growth (59,60) it is likely that these pathways converge on common events affecting cell growth, architecture, and metabolic requirements. We previously demonstrated that several hypertrophic stimuli, including AngII, isoproterenol, prostaglandin F 2␣ , insulin-like growth factor-1, and 1,25-dihydroxyvitamin D 3 , are capable of inducing cell growth without division in C2C12 myoblasts and that all of these result in Rb phosphorylation specifically at serine 780 (10).…”

Distribution of transforming growth factor-beta 1, fibronectin, and smooth muscle actin in asbestos-induced pulmonary fibrosis in rats.

“…It is clear that TGFP and other factors can affect contractile cells and proteins in a variety of cell types (Mitchell et al, 1993). TGFP has been shown to up-regulate a-smooth muscle actin in cardiac myocytes (Parker et al, 1990) and smooth muscle cells (Bjorkerud, 1991) but not in fibroblasts (Rubbia-Brandt et al, 1991). It is feasible that the local increase in smooth muscle actin found at first alveolar duct bifurcations could be a result of paracrine stimulation by the E F P produced by alveolar macrophages accumulating on the surfaces of the bifurcations.…”

“…In addition to stimulation of extracellular matrix production, TGFD stimulates proliferation of certain types of mesenchymal cells (Moses et al, 1987) and can be chemotactic for fibroblasts (Roberts and Spom, 1990). TGFB also enhances the expression of a-smooth muscle actin in cultured myocytes and smooth muscle cells (Bjorkerud, 1991;Parker et al, 1990). Expression of a-smooth muscle actin increases in bleomycin-induced fibrosis of rat lung (Mitchell et al, 1989).…”

TGF-β signaling in vascular biology and dysfunction

“…Indeed, losartan has been approved for the reduction of cardiovascular events in patients with hypertension and left ventricular hypertrophy [112]. Furthermore it has been reported that TGF-β stimulation alters the program of differentiation-related gene expression in isolated cardiac myocytes, promoting the synthesis of fetal contractile proteins, characteristic of pressure-overload hypertrophy [113]. Over-expression of TGF-β in transgenic mice results in cardiac hypertrophy which is characterized by both interstitial fibrosis and hypertrophic growth of cardiac myocytes [114].…”