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Publication : Differential regulation of vitronectin in mice and humans in vitro.

First Author  Seiffert D Year  1996
Journal  J Biol Chem Volume  271
Issue  10 Pages  5474-80
PubMed ID  8621404 Mgi Jnum  J:31859
Mgi Id  MGI:79362 Doi  10.1074/jbc.271.10.5474
Citation  Seiffert D, et al. (1996) Differential regulation of vitronectin in mice and humans in vitro. J Biol Chem 271(10):5474-80
abstractText  To define the cis-acting elements involved in the regulation of the murine vitronectin (Vn) gene in inflammation, the 5'-flanking region was isolated, fused to the luciferase reporter gene, and the basal and interleukin 6 (IL-6)-stimulated transcriptional activity was tested in transfection experiments using Hep3B cells. Treatment with IL-6 induced this construct by more than 20-fold, whereas the corresponding 5'-flanking region of the human Vn gene was not stimulated. Transfection studies using murine Vn constructs with serial 5'-deletions revealed that two sequences were important in the IL-6 response, and specific mutations in both sequences abolished the response. A 2-base pair mutation converted the human sequence to that of a murine IL-6 responsive element and partially conveyed IL-6 inducibility. In contrast, transforming growth factor beta stimulated the human construct and the endogenous Vn gene in human Hep3B cells in a dose-dependent manner, whereas the murine construct was not responsive. The transforming growth factor beta responsive region was localized to a 30-base pair fragment with little homology to the murine sequence. These studies reveal that the structural basis for the differential regulation of the human and murine Vn genes resides in the differences in promoter sequence.
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