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PMID: 1688886 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 85 ·No. 2 ·1990-02-00 ·Pages 507-14

Parker TG, Packer SE, Schneider MD

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-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.

MeSH Terms
Actins/genetics Animals Animals, Newborn/metabolism Cardiomegaly/etiology Cell Differentiation Cells, Cultured Fibroblast Growth Factors/pharmacology Gene Expression Regulation/drug effects Major Histocompatibility Complex Myocardium/metabolism Myosins/genetics RNA/analysis Rats Rats, Inbred Strains Transforming Growth Factors/pharmacology
Chemicals
Actins Fibroblast Growth Factors RNA Transforming Growth Factors Myosins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Parker T G
Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Packer S E
Schneider M D
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
Published
1990-02-00
Pages
507-14
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC296452
Subset
IM
Grants
NHLBI NIH HHS · HL-39141 · United States
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