COLLAGEN PRODUCTION AND REPLICATION BY CARDIAC FIBROBLASTS IS ENHANCED IN RESPONSE TO DIVERSE CLASSES OF GROWTH-FACTORS

The tissue distribution and cellular effects of platelet-derived growt h factor (PDGF), basic frbroblast growth factor (bFGF), transforming g rowth factor beta-1 (TGF beta(1)) and insulin-like growth factor 1 (IG F-1) suggest a potential role for these factors in cardiovascular matr ix deposition. The objective of this study was to assess the capacity of these growth factors to promote cardiac fibroblast collagen product ion and replication in vitro which will lead to studies identifying th eir role in vivo during cardiac development and disease. Fibroblasts w ere isolated from fetal rat hearts by explant culture, and their respo nse to growth factors was assessed with respect to fibroblast replicat ion and collagen synthesis. Fibroblast replication was stimulated by P DGF and by bFGF. IGF-1 and TGF beta(1) had no effect on fibroblast rep lication. Collagen production was stimulated by all of the growth fact ors tested in order of potency TGF beta(1) > PDGF, IGF > bFGF. None of the growth factors affected the proportion of newly synthesized colla gen rapidly degraded. We have shown that TGF beta(1), PDGF, bFGF and I GF-1 are all capable of increasing collagen deposition by cardiac fibr oblasts by either stimulating fibroblast replication or collagen synth esis or both. The sensitivity of cardiac fibroblasts to these factors is consistent with their playing a role in the rapid changes in cardia c collagen deposition seen during development and disease.