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PMID: 2402491 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Differential regulation of skeletal alpha-actin transcription in cardiac muscle by two fibroblast growth factors.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 18 ·1990-09-00 ·Pages 7066-70

Parker TG, Chow KL, Schwartz RJ, Schneider MD

Abstract

In cardiac muscle, acidic and basic fibroblast growth factors (aFGF and bFGF) regulate at least five genes in common (including alpha and beta myosin heavy chains, atrial natriuretic factor, and the sarcoplasmic reticulum calcium ATPase), provoking a generalized "fetal" phenotype similar to events in pressure-overload hypertrophy; however, aFGF and bFGF differentially control the striated alpha-actins. bFGF stimulates and aFGF inhibits skeletal alpha-actin transcripts associated with the embryonic heart, whereas cardiac alpha-actin mRNA is inhibited by aFGF but not bFGF. To elucidate mechanisms for these selective and discordant actions of aFGF and bFGF on cardiac muscle, chicken skeletal and cardiac alpha-actin promoter-driven reporter genes were introduced into neonatal rat cardiac myocytes by electroporation. Skeletal alpha-actin transcription was selectively stimulated by bFGF, whereas the cardiac alpha-actin promoter was unaffected. In contrast, aFGF suppressed both transfected alpha-actin genes. The differential regulation of skeletal alpha-actin transcription was equivalent with either purified or recombinant FGFs and was observed with 5' flanking sequences from either nucleotide -202 or -2000 to nucleotide -11. Positive and negative modulation of alpha-actin transcription by growth factors corresponded accurately to the endogenous genes in all permutations studied. These investigations provide a model for reciprocal control of gene transcription by aFGF vs. bFGF.

MeSH Terms
Actins/genetics Animals Cells, Cultured Chloramphenicol O-Acetyltransferase/genetics Fibroblast Growth Factors/pharmacology Gene Expression Regulation/drug effects Genes/drug effects Muscles/metabolism Myocardium/metabolism Promoter Regions, Genetic Rats Rats, Inbred Strains Transcription, Genetic/drug effects Transfection
Chemicals
Actins Fibroblast Growth Factors Chloramphenicol O-Acetyltransferase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Parker T G
Molecular Cardiology Unit, Baylor College of Medicine, Houston, TX 77030.
Chow K L
Schwartz R J
Schneider M D
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51 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.18.7066
Published
1990-09-00
Pages
7066-70
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC54684
Subset
IM
Grants
NHLBI NIH HHS · P50-HL42267 · United States
NHLBI NIH HHS · R01-HL38401 · United States
External Links
PubMed source DOI: 10.1073/pnas.87.18.7066 PMC Full Text View journal details
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