FIBROBLAST GROWTH FACTOR-II STIMULATES EMBRYONIC CARDIAC MESENCHYMAL CELL-PROLIFERATION

The proliferation response of stage chick atrioventricular valve mesen chymal cells to fibroblast growth factor-a (FGF-S) was studied in the tissue-like environment of three-dimensional cell aggregates maintaine d in organ culture, The mitogenic effects of FGF-S on mesenchymal tiss ue depended on the FGF-2-stimulated formation of a fibronectin-contain ing extracellular matrix, The matrix was absent in unstimulated aggreg ates, and co-localized with regions of actively proliferating cells in stimulated aggregates, Inhibition of fibronectin matrix formation by the inclusion of Arg-Gly-Asp-containing peptides, which compete with f ibronectin for binding to the cell surface alpha(5) beta(1) integrin r eceptors, abolished the proliferation effects of FGF-2. Inhibition of sulfation of cell surface glycosaminoglycans by treatment with sodium chlorate significantly reduced both the formation of the fibronectin m atrix and cell proliferation in response to FGF-S, suggesting an invol vement of the low-affinity sulfated glycosaminoglycan FGF receptor sys tem, Thus, the FGF-stimulated growth of embryonic atrioventricular val ve mesenchyme in vitro involves the production of a fibronectin matrix . We suggest that the stimulation of the fibronectin matrix represents an essential element in growth factor signaling of mesenchymal tissue , with the matrix serving as an anchorage substratum for the prolifera ting cells. (C) 1996 Wiley-Liss, Inc.