Platelet-derived growth factor and epidermal growth factor play a major role in human colonic fibroblast repair activities

Background and Aims: Ulceration is a com mon feature of inflammatory bowel diseases, where subepithelial cell growth is frequently necessary for resolution. In order to further understand the role of colonic fibroblasts in this process, we have used an in vitro model of wound repair to study the response of human colonic fibroblasts to several growth factors expressed in colonic tissues. Methods: Proliferation was determined by [H-3]thymidine incorporation into DNA in subconfluent fibroblast cultures. In vitro wound repair was determined in confluent fibroblast monolayers after mechanical denudation, The presence of growth factors secreted by fibroblasts was studied in conditioned medium by heparin affinity chromatography and immunodetection with specific antibodies. Results: Serum and platelet-derived growth factor (PDGF-BB) induced a dramatic increase in both colonic fibroblast proliferation and closure of wounded cell monolayers. Epidermal growth factor (EGF) stimulated both fibroblast activities, but the effect was less potent. However, colon ic fibroblasts did not respond to transforming growth factor-pi. Conditioned medium stimulated fibroblast proliferation and wound repair activity, which was reverted by the addition of suramin. furthermore, a PDGF-like factor was isolated from colonic fibroblast-conditioned medium. Conclusions: EGF and PDGF-BB promote human colonic fibroblast-dependent wound repair activities. Human colonic fibroblasts may exert an autocrine regulation via the production of growth factors. Copyright (C) 2000 S. Karger AG, Basel.