BASIC FIBROBLAST GROWTH-FACTOR IN THE EXTRACELLULAR-MATRIX SUPPRESSESCOLLAGEN-SYNTHESIS AND TYPE-III PROCOLLAGEN MESSENGER-RNA LEVELS IN ARTERIAL SMOOTH-MUSCLE CELL-CULTURES

To determine the effects of an intact extracellular matrix on collagen synthesis, arterial smooth muscle cells (SMCs) were plated sparsely o n a cell-free, SMC-derived matrix and examined the following day. Coll agen synthesis during a 5-hour incubation by cells on the matrix was r educed to 67% of the control values obtained from cultures on plastic. Total protein synthesis was unaffected. Treatment of the matrix with heparitinase to remove basic fibroblast growth factor (bFGF) before se eding the SMCs abolished the inhibitory effect of the matrix on collag en synthesis. The inhibitory effect was also eliminated by treating th e matrix with a neutralizing polyclonal antibody directed against bFGF . Collagen synthesis by SMC cultures grown in wells coated with purifi ed bFGF was only 61% that of control cultures, whereas total protein s ynthesis remained unchanged. Slot-blot analysis revealed that the rela tive message level for alpha1(III) procollagen was reduced in cultures grown on the preexisting matrix or on plastic precoated with bFGF, wh ereas the alpha1(I) procollagen message was unaffected. These results demonstrate the ability of the extracellular matrix to modulate the sy nthesis of collagen by arterial SMCs and indicate that bFGF in the mat rix is responsible for these effects.