Collagen production and replication by cardiac fibroblasts is enhanced in response to diverse classes of growth factors

Abstract

The tissue distribution and cellular effects of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), transforming growth factor beta-1 (TGF beta 1) and insulin-like growth factor 1 (IGF-1) suggest a potential role for these factors in cardiovascular matrix deposition. The objective of this study was to assess the capacity of these growth factors to promote cardiac fibroblast collagen production and replication in vitro which will lead to studies identifying their role in vivo during cardiac development and disease. Fibroblasts were isolated from fetal rat hearts by explant culture, and their response to growth factors was assessed with respect to fibroblast replication and collagen synthesis. Fibroblast replication was stimulated by PDGF and by bFGF.IGF-1 and TGF beta 1 had no effect on fibroblast replication. Collagen production was stimulated by all of the growth factors tested in order of potency TGF beta 1 > PDGF, IGF > bFGF. None of the growth factors affected the proportion of newly synthesized collagen rapidly degraded. We have shown that TGF beta 1, PDGF, bFGF and IGF-1 are all capable of increasing collagen deposition by cardiac fibroblasts by either stimulating fibroblast replication or collagen synthesis or both. The sensitivity of cardiac fibroblasts to these factors is consistent with their playing a role in the rapid changes in cardiac collagen deposition seen during development and disease.