EFFECT OF TRANSFORMING GROWTH-FACTOR-BETA-1 AND BASIC FIBROBLAST GROWTH-FACTOR ON THE EXPRESSION OF CELL-SURFACE PROTEOGLYCANS IN HUMAN LUNG FIBROBLASTS - ENHANCED GLYCANATION AND FIBRONECTIN-BINDING OF CD44 PROTEOGLYCAN, AND DOWN-REGULATION OF GLYPICAN

We have tested the effects of transforming growth factor-beta 1 (TGF-b eta 1), basic fibroblast growth factor (bFGF) and TGF-beta 1 + bFGF on the expression of the cell surface proteoglycans (CD44, syndecans and glypican) in cultures of human lung fibroblasts (HLF). Cell surface p roteoglycan expression was monitored by quantitative immunoprecipitati on from metabolically labelled cells, Western and Northern blotting an d evaluation of the glycanation of the proteoglycans. Stimulation of t he cells with TGF-beta 1 increased the length of the chondroitin sulph ate (CS) chains on CD44 (similar to 1.6-fold). bFGF, administered sole ly, also increased the length of the CS chains on CD44 (similar to 1.4 -fold), whereas the combination of TGF-beta 1 + bFGF nearly doubled bo th the length and the number of the CS chains on CD44. None of these t reatments lead to changes in CD44 message or core-protein expression. This enhanced glycanation of CD44 after the TGF-beta 1, bFGF and combi ned treatments correlated with a 2-fold increase in the affinity of th e proteoglycan for fibronectin but had no influence on the binding to type I collagen. TGF-beta 1, alone or in combination with bFGF, also s timulated the CS content of syndecan-1, but none of the other syndecan s was significantly affected by any of the factors or combinations tes ted. The expression of glypican however was significantly decreased (n early halved) by the combination of TGF-beta 1 + bFGF, less so by TGF- beta 1 and not at all by bFGF. This decrease occurred both at the leve l of the message and of the core protein. These data demonstrate speci fic and differential effects of TGF-beta 1 and bFGF on the structure, expression and interactions of the cell surface proteoglycans of HLF.