Fibroblast proliferation during myocardial development in rats is regulated by IGF-1 receptors.
To determine whether the growth of cardiac fibroblasts during development is modulated by the insulin-like growth factor (IGF)-1 receptor (IGF-1R), the expression of IGF-1, IGF-2, and IGF-1R was determined in fibroblasts from fetal and postnatal hearts. The expression of proliferating cell nuclear antigen (PCNA) and DNA polymerase-alpha was also evaluated in combination with the estimation of DNA replication. In comparison with fetal hearts, at postnatal day 21, fibroblast expression of IGF-1R mRNA, IGF-2, PCNA, and DNA polymerase-alpha was reduced by 77, 70, 80, and 86%, respectively. Moreover, IGF-1R protein decreased by 48% at 21 days. Bromodeoxyuridine labeling decreased by 88 and 89% in the left and right ventricle, respectively, at this time. Two different antisense oligodeoxynucleotides to IGF-1R reduced DNA replication by 60 and 44% in fibroblasts in culture. In addition, this intervention markedly attenuated the growth response of fibroblasts to IGF-1 or serum. In conclusion, the IGF-1R system appears to play a major role in the regulation of fibroblast growth in the heart in vivo.
Reiss
K
K
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Cheng
W
W
Kajstura
J
J
Sonnenblick
E H
EH
Meggs
L G
LG
Anversa
P
P
D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development*; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004257:DNA Polymerase II / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005347:Fibroblasts / Q000166:cytology; D006321:Heart / Q000196:embryology*; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology*; D015345:Oligonucleotide Probes / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000502:physiology*; D013002:Somatomedins / Q000378:metabolism
D016375:Antisense Elements (Genetics); D015345:Oligonucleotide Probes; D018809:Proliferating Cell Nuclear Antigen; D013002:Somatomedins; D004247:DNA; D017526:Receptor, IGF Type 1; D004257:DNA Polymerase II