Identification and characterization of high glucose and glucosamine responsive element in the rat osteopontin promoter

Autor: Ayako Take, Koutaro Yokote, Seijiro Mori, Amy L. Ridall, Kazuki Kobayashi, Sunao Asaumi, Harukiyo Kawamura, Minoru Takemoto, Masaki Fujimoto, William T. Butler, Yasushi Saito
Rok vydání: 2003
Předmět:
Zdroj: Journal of Diabetes and its Complications. 17:34-38
ISSN: 1056-8727
DOI: 10.1016/s1056-8727(02)00189-7
Popis: We have previously reported that high glucose stimulates osteopontin (OPN) expression via a protein kinase C-dependent pathway and a hexosamine pathway in cultured rat aortic smooth muscle cells (SMCs) [Biochem. Biophys. Res. Commun. 258 (1999) 722.]. In the present study, we carried out functional OPN promoter assays using the luciferase expression vector system in cultured rat aortic SMCs to determine a high glucose/glucosamine responsive element. An extensive deletion analysis of the 5′-flanking region of the rat OPN gene revealed that an element involved in high glucose and glucosamine responses was present within a region between −112 and −62 bp of the OPN promoter. This region is highly conserved in the rat, mouse, and human promoters and contains a number of consensus regions, including an E-box and a GC-rich region. Mutation of the E-box or the GC-rich region resulted in a significant loss of both high glucose and glucosamine responses. These results suggest that two cis-acting elements, the E-box and the GC-rich region, are involved at least partly in high glucose/glucosamine-stimulated transcription of the rat OPN gene.
Databáze: OpenAIRE