FIBROBLAST PROLIFERATION DURING MYOCARDIAL DEVELOPMENT IN RATS IS REGULATED BY IGF-1 RECEPTORS

To determine whether the growth of cardiac fibroblasts during developm ent is modulated by the insulin-like growth factor (IGF)-1 receptor (I GF-IR), the expression of IGF-I, IGF-2, and IGF-IR was determined in f ibroblasts from fetal and postnatal hearts. The expression of prolifer ating cell nuclear antigen (PCNA) and DNA polymerase-alpha was also ev aluated in combination with the estimation of DNA replication. In comp arison with fetal hearts, at postnatal day 21, fibroblast expression o f IGF-1R mRNA, IGF-2, PCNA, and DNA polymerase-cu was reduced by 77, 7 0, 80, and 86%, respectively. Moreover, IGF-1R protein decreased by 48 % at 21 days. Bromodeoxyuridine labeling decreased by 88 and 89% in th e left and right ventricle, respectively, at this time. Two different antisense oligodeoxynucleotides to IGF-1R reduced DNA replication by 6 0 and 44% in fibroblasts in culture. In addition, this intervention ma rkedly 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.