BASIC FGF REGULATES INTERSTITIAL COLLAGENASE GENE-EXPRESSION IN HUMANSMOOTH-MUSCLE CELLS

Basic fibroblast growth factor (bFGF) is a mitogenic factor that is im plicated in smooth muscle cell growth in atherosclerosis and vascular restenosis. In this study, we examined the effect of bFGF on the expre ssion of the interstitial collagenase gene in human vascular smooth mu scle cells. Results from Northern transfer analysis showed that bFGF i ncreased collagenase mRNA levels greater than threefold as early as 24 h. Collagenase pre-mRNA revels were elevated approximately threefold by bFGF, according to RT-PCR analysis. Transient transfections of the smooth muscle cells with a 4.4-kb human collagenase promoter-CAT repor ter gene, however, failed to show upregulation of the promoter activit y by bFGF. Interestingly, transfections with deleted fragments contain ing promoter sequences from -1047 to -2271 resulted in modest stimulat ion of the collagenase-CAT promoter activity by bFGF. bFGF did not alt er the stability of the collagenase mRNA, as demonstrated by degradati on studies. The enhanced collagenase mRNA levels elicited by bFGF were reflected in increased amounts of collagenase protein that were detec ted by Western blot analysis. In summary, bFGF upregulates the interst itial collagenase expression, resulting in turnover of the extracellul ar matrix, an event that could facilitate smooth muscle cell migration and proliferation during the early stages of atherosclerosis and rest enosis. (C) 1997 Wiley-Liss, Inc.