Differential regulation of collagenase and type I collagen gene expression by basic fibroblast growth factor in human smooth muscle cells

Susan Heather Kennedy, Thomas Jefferson University

Abstract

Basic fibroblast growth factor (bFGF) is a mitogenic factor that is implicated in smooth muscle cell growth associated with atherosclerosis and restenosis. In this study, we have examined other biologic effects of bFGF, specifically, its effect on the expression of interstitial collagenase and type I collagen genes in human vascular smooth muscle cells (SMC). Results from Northern transfer showed that bFGF increased collagenase mRNA levels substantially, as early as 24 hours after incubation. RT-PCR, and nuclear run-on analyses demonstrated that bFGF upregulated collagenase expression via enhanced transcription of the gene. Collagenase promoter activity was elevated several-fold by bFGF in stable-transfectant cells. In contrast, bFGF reduced type I collagen gene expression as shown by decreased pro-$\alpha$1(I) type I collagen mRNA levels. RT-PCR and nuclear run-on analyses did not show alterations in the transcription rate of the pro-$\alpha$1(I) gene. The inhibition of type I collagen gene expression by bFGF is apparently mediated at the post-transcriptional level, as reflected by enhanced degradation of the mRNA transcripts. In summary, bFGF has the capability to elicit turnover of the extracellular matrix, an event that could facilitate smooth muscle cells migration and proliferation during early stages of atherosclerosis and restenosis.

Subject Area

Cellular biology|Molecular biology

Recommended Citation

Kennedy, Susan Heather, "Differential regulation of collagenase and type I collagen gene expression by basic fibroblast growth factor in human smooth muscle cells" (1996). ETD Collection for Thomas Jefferson University. AAI9625289.
https://jdc.jefferson.edu/dissertations/AAI9625289

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