Fibroblast proliferation during myocardial development in the rat
is regulated by insulin-like growth factor-1 receptors.
Reiss, Krzysztof, Wei Cheng, Jan Kajstura, Edmund H. Sonnenblick,
Leonard G. Meggs, and Piero Anversa.
Department of Medicine, New York Medical College, Valhalla, New
York 10595; and Division of Cardiology, Department of Medicine,
Albert Einstein College of Medicine, Bronx, New York 10461
APStracts 2:0093H, 1995.
To determine whether the growth of cardiac fibroblasts during
development is modulated by the 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 day 21 postnatally, IGF-1R mRNA in fibroblasts
was reduced by 77%, IGF-2 by 70%, PCNA by 80% and DNA polymerase
[alpha] by 86%. Moreover, IGF-1R receptor protein decreased by 48% at
21 days. Bromodeoxyuridine labeling decreased by 88% in the left
ventricle and 89% in the right ventricle at this time. Two different
antisense oligodeoxynucleotides to IGF-1R reduced by 60% and 44% DNA
replication 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 receptor system appears to play a
major role in the regulation of fibroblast growth in the heart in
vivo.
Received 17 June 1994; accepted in final form 2 March 1995.
APS Manuscript Number H539-4.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.