BASIC FIBROBLAST GROWTH-FACTOR STIMULATES HEPATOCYTE GROWTH-FACTOR SCATTER FACTOR SECRETION BY HUMAN MESENCHYMAL CELLS

Basic fibroblast growth factor (bFGF) together with other pleiotropic factors plays an important role in many complex physiological processe s such as embryonic development, angiogenesis, and wound repair. Among these factors, hepatocyte growth factor/scatter factor (HGF/SF) which is secreted by cells of mesodermal origin exerts its mito- and motoge nic activities on cells of epithelial and endothelial origin. Knowledg e of the regulatory mechanisms of HGF/SF may contribute to the underst anding of its role in physio-pathological processes. We observed that the secretion of HGF/SF by MRC-5 cells and by other fibroblast-derived cell cultures in conditioned media was enhanced by exposure to bFGF. HGF/SF was measured by the scatter assay, a bioassay for cell motility , and was further characterized by Western blot analysis with anti-HGF /SF antibodies. Exposure of MRC-5 cultures to 10 ng/ml of bFGF resulte d already 6 h posttreatment in a threefold higher amount of scatter fa ctor secreted into the medium as compared to untreated cultures. HGF/S F secretion was sustained after bFGF treatment for the following 72 h when increased amounts of HGF/SF were detected both in conditioned med ia as well as associated to the extracellular matrix. The secretion of HGF/SF in cell supernatants increased dose dependently upon treatment with bFGF starting from basal levels of 6 U/ml and reaching 27 U/ml a t 30 ng/ml bFGF, plateauing thereafter. Upregulation of HGF/SF by IL-l , already described by others, was confirmed in this study. Based on o ur findings an articulated interaction can be speculated for bFGF, HGF /SF, and IL-l,e.g., in tissue regeneration during inflammatory process es or in wound healing. (C) 1996 Wiley-Liss, Inc.