Transforming growth factor-beta 1 increases internalization of basic fibroblast growth factor by smooth muscle cells: implication of cell-surface heparan sulphate proteoglycan endocytosis.
Basic fibroblast growth factor (bFGF) was internalized by smooth muscle cells (SMC) from pig aorta. Correlation between heparin inhibition of binding and late internalization (8 h) 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, 35S-labelled proteoglycans of the extracellular matrix (ECM) were not affected. This might be explained by the different turnover rates displayed by the two populations of proteoglycans. Although bFGF and/or TGF-beta 1 induced a similar stimulation in cell-surface chondroitin sulphate/dermatan sulphate and heparan sulphate (HS) proteoglycan synthesis, only the turnover of HS proteoglycans was increased. Twice as much HS proteoglycan was internalized in the presence of TGF-beta 1 or bFGF. Furthermore, TGF-beta 1 induced a 43 +/- 12% increase in HS proteoglycan internalized in the presence of bFGF with a parallel 38% increase in bFGF internalization. Overall, the results indicated that bFGF bound to two HS proteoglycan populations. bFGF storage (70% of bFGF bound to SMC) was not affected by TGF-beta 1 under our conditions and involved ECM proteoglycans characterized by a low turnover. bFGF internalization up-regulated by TGF-beta 1 involved cell-surface HS proteoglycan characterized by a high turnover.
D000818:Animals; D001013:Aorta, Thoracic; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D006497:Heparan Sulfate / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D013552:Swine; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D015854:Up-Regulation
D016326:Extracellular Matrix Proteins; D016222:Fibroblast Growth Factor 2; D006497:Heparan Sulfate; D008565:Membrane Proteins; D011509:Proteoglycans; D016212:Transforming Growth Factor beta