Postnatal regulation of fibroblast growth factor ligand and receptor gene expression in rat thoracic aorta.
Fibroblast growth factor (FGF)-1 and FGF-2 are potent angiogenic factors and vascular smooth muscle cell (SMC) mitogens in vivo. They function via binding to a family of structurally related cell surface receptors that possess intrinsic tyrosine kinase activity. Several studies have indicated that increased FGF and/or FGF receptor (FGFR) expression may correlate with adult SMC proliferation in vivo. In this study, we used Northern blot hybridization and reverse transcription-polymerase chain reaction assays to compare the FGF and FGFR mRNA levels in newborn rat aorta, where SMCs have a high replication index, to those in adult rat aorta, where SMCs are relatively quiescent. We found that FGF-2 and FGFR-2 mRNA expression was elevated 8.2- and 5.6-fold, respectively, in adult aorta. Increased FGF-2 protein expression in the adult aorta was confirmed by Western blot analysis. We also examined FGF and FGFR mRNA expression levels in SMC cultures derived from newborn or adult rat aorta. FGF-1 transcripts were more abundant in newborn SMCs whereas FGF-2 and FGFR-1 mRNA expression was higher in adult SMCs. Furthermore, FGF-1 and FGF-2 mRNA expression levels were altered by cell culture density and by serum treatment. We conclude that elevated FGF ligand and receptor expression does not always correlate with a high SMC proliferative index, that FGF-1 or FGF-2 may not be the primary mitogens responsible for newborn SMC growth in vivo, and that FGF-1 and FGF-2 may serve nonmitogenic functions within the mature, adult vessel wall.
Winkles
J A
JA
Department of Molecular Biology, Holland Laboratory, American Red Cross, Rockville, Maryland 20855, USA.
Alberts
G F
GF
Peifley
K A
KA
Nomoto
K
K
Liau
G
G
Majesky
M W
MW
D000818:Animals; D000831:Animals, Newborn; D001013:Aorta, Thoracic / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D001483:Base Sequence / Q000235:genetics; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D008024:Ligands; D009130:Muscle, Smooth / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism
D008024:Ligands; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D016222:Fibroblast Growth Factor 2; D005346:Fibroblast Growth Factors