TRANSFORMING GROWTH-FACTOR-BETA-1 INCREASES INTERNALIZATION OF BASIC FIBROBLAST GROWTH-FACTOR BY SMOOTH-MUSCLE CELLS - IMPLICATION OF CELL-SURFACE HEPARAN-SULFATE PROTEOGLYCAN ENDOCYTOSIS

Basic fibroblast growth factor (bFGF) was internalized by smooth muscl e cells (SMC) from pig aorta. Correlation between heparin inhibition o f binding and late internalization (8h) implicated low-affinity sites in bFGF internalization. Transforming growth factor-beta 1 (TGF-beta 1 ) induced a 38% increase in bFGF internalized between 4 and 8 h. While bFGF and/or TGF-beta 1 enhanced cell-surface proteoglycan synthesis, S-35-labelled proteoglycans of the extracellular matrix (ECM) were not affected. This might be explained by the different turnover rates dis played by the two populations of proteoglycans. Although bFGF and/or T GF-beta 1 induced a similar stimulation in cell-surface chondroitin su lphate/dermatan sulphate and heparan sulphate (HS) proteoglycan synthe sis, only the turnover of HS proteoglycans was increased. Twice as muc h HS proteoglycan was internalized in the presence of TGF-beta 1 or bF GF. Furthermore, TGF-beta 1 induced a 43+/-12% increase in HS proteogl ycan internalized in the presence of bFGF with a parallel 38% increase in bFGF internalization. Overall, the results indicated that bFGF bou nd to two HS proteoglycan populations. bFGF storage (70% of bFGF bound to SMC) was not affected by TGF-beta 1 under our conditions and invol ved ECM proteoglycans characterized by a low turnover. bFGF internaliz ation up-regulated by TGF-beta 1 involved cell-surface HS proteoglycan characterized by a high turnover.