Upstream Stimulatory Factor 1 Regulates Osteopontin Expression in Smooth Muscle Cells
| Autor: | Uriel M. Malyankar, Stephen M. Schwartz, R. Hanson, Cecilia M. Giachelli, A. L. Ridall |
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| Rok vydání: | 1999 |
| Předmět: |
Aging
Vascular smooth muscle Transcription Genetic Sialoglycoproteins Oligonucleotides USF1 Response Elements Transfection Muscle Smooth Vascular Upstream Stimulatory Factor stomatognathic system Consensus Sequence Gene expression Transcriptional regulation Animals RNA Messenger Osteopontin Promoter Regions Genetic Transcription factor Cells Cultured Regulation of gene expression Base Sequence biology Cell Biology Molecular biology Rats DNA-Binding Proteins Carotid Arteries Animals Newborn Gene Expression Regulation Mutation biology.protein Upstream Stimulatory Factors Carotid Artery Injuries Angioplasty Balloon Transcription Factors |
| Zdroj: | Experimental Cell Research. 250:535-547 |
| ISSN: | 0014-4827 |
| DOI: | 10.1006/excr.1999.4537 |
| Popis: | Vascular smooth muscle cells (SMCs) undergo a dramatic phenotypic transition in response to injury and ex vivo culture that includes enhanced proliferation, migration, matrix deposition, and alterations in gene expression. Osteopontin is a good marker for the injury-induced SMC phenotypic state in vivo and in vitro. To identify transcription factors that might control the regulation of osteopontin expression, we investigated cultured vascular SMCs that express high and low levels of osteopontin. Using nuclear run-on assays, mRNA stability studies, and deletion analysis, we demonstrate that regulation of osteopontin steady-state mRNA levels in SMCs occurs at the transcriptional level. Transient transfection and gel-shift analyses of osteopontin promoter indicated that a region between -123 and +66 was involved in the expression of osteopontin. Supershift EMSAs identified the bHLH-leucine zipper transcription factor upstream stimulatory factor-1 (USF1) as the protein binding to this sequence. Finally, we show that USF1 protein is induced in vivo within 24 h of balloon angioplasty of rat carotids coordinately with osteopontin induction. These data suggest that USF1 governs expression of osteopontin in cultured vascular SMCs and might contribute to initial osteopontin expression observed post carotid injury and in vascular pathologies in vivo. |
| Databáze: | OpenAIRE |
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