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PMID: 8098844 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Molecular cloning of a diverged homeobox gene that is rapidly down-regulated during the G0/G1 transition in vascular smooth muscle cells.

Molecular and cellular biology ·Vol. 13 ·No. 6 ·1993-06-00 ·Pages 3722-33

Gorski DH, LePage DF, Patel CV, Copeland NG, Jenkins NA, Walsh K

Abstract

Adult vascular smooth muscle cells dedifferentiate and reenter the cell cycle in response to growth factor stimulation. Here we describe the molecular cloning from vascular smooth muscle, the structure, and the chromosomal location of a diverged homeobox gene, Gax, whose expression is largely confined to the cardiovascular tissues of the adult. In quiescent adult rat vascular smooth muscle cells, Gax mRNA levels are down-regulated as much as 15-fold within 2 h when these cells are induced to proliferate with platelet-derived growth factor (PDGF) or serum growth factors. This reduction in Gax mRNA is transient, with levels beginning to rise between 8 and 24 h after mitogen stimulation and returning to near normal by 24 to 48 h. The Gax down-regulation is dose dependent and can be correlated with the mitogen's ability to stimulate DNA synthesis. PDGF-AA, a weak mitogen for rat vascular smooth muscle cells, did not affect Gax transcript levels, while PDGF-AB and -BB, potent mitogens for these cells, were nearly as effective as fetal bovine serum. The removal of serum from growing cells induced Gax expression fivefold within 24 h. These data suggest that Gax is likely to have a regulatory function in the G0-to-G1 transition of the cell cycle in vascular smooth muscle cells.

MeSH Terms
Animals Aorta/cytology,physiology Base Sequence Cell Cycle/physiology Chromosome Mapping Cloning, Molecular Crosses, Genetic DNA/genetics,isolation & purification Female G1 Phase Gene Library Genes, Homeobox/drug effects Genetic Variation Homeodomain Proteins Humans Kinetics Male Mice Mice, Inbred C57BL Molecular Sequence Data Muridae Muscle Proteins/genetics Muscle, Smooth, Vascular/cytology,physiology Oligodeoxyribonucleotides Platelet-Derived Growth Factor/pharmacology Rats Resting Phase, Cell Cycle Sequence Homology, Amino Acid Thymidine/metabolism
Chemicals
Homeodomain Proteins Meox2 protein, rat Muscle Proteins Oligodeoxyribonucleotides Platelet-Derived Growth Factor DNA Thymidine
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Gorski D H
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
LePage D F
Patel C V
Copeland N G
Jenkins N A
Walsh K
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1993-06-00
Pages
3722-33
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC359848
Subset
IM
Grants
NIAMS NIH HHS · AR40197 · United States
NHLBI NIH HHS · HL45345 · United States
NCI NIH HHS · N01-CO-74101 · United States
Databases
GENBANK
Z17223
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