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Bontemps Y Vuillermoz B Antonicelli F Perreau C Danan JL Maquart FX Wegrowski Y 《The Journal of biological chemistry》2003,278(24):21566-21575
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UDP-glucose dehydrogenase (UGDH) catalyzes the formation of UDP-glucuronate. Glucuronate represents an integral component of the glycosaminoglycan, hyaluronan, which accumulates in orbital Graves disease. Here we report that orbital fibroblasts express higher levels of UGDH than do those from skin. This is a consequence of greater UGDH gene promoter activity and more abundant steady-state UGDH mRNA. Six Sp1 sites located in the proximal 550 bp of the UGDH gene promoter appear to determine basal promoter activity, as does a previously unrecognized 49-bp sequence spanning -1436 nucleotides (nt) and -1388 nt that negatively affects activity. Nuclear Sp1 protein is more abundant in orbital fibroblasts, and its binding to specific sites on DNA is greater than that in dermal fibroblasts. Mutating each of these Sp1 sites in a UGDH gene promoter fragment, extending from -1387 to +71 nt and fused to a luciferase reporter, results in divergent activities when transfected in orbital and dermal fibroblasts. Reducing Sp1 attenuated UGDH gene promoter activity, lowered steady-state UGDH mRNA levels, and reduced UGDH enzyme activity. Targeting Sp1 and UGDH with specific siRNAs also lowered hyaluronan synthase-1 (HAS-1) and HAS-2 levels and reduced hyaluronan accumulation in orbital fibroblasts. These findings suggest that orbital fibroblasts express high levels of UGDH in an anatomic-specific manner, apparently the result of greater constitutive Sp1. These high UGDH levels may underlie susceptibility of the orbit to localized overproduction of hyaluronan in Graves disease. 相似文献
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Identification of regulatory elements within the minimal promoter region of the human endogenous ERV9 proviruses: accurate transcription initiation is controlled by an Inr-like element.
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G La Mantia B Majello A Di Cristofano M Strazzullo G Minchiotti L Lania 《Nucleic acids research》1992,20(16):4129-4136
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Wenfang Liu Geping Wang Alexander G Yakovlev 《The Journal of biological chemistry》2002,277(10):8273-8278
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Role of the Sp family of transcription factors in the ontogeny of growth hormone receptor gene expression 总被引:2,自引:0,他引:2
Yu JH Schwartzbauer G Kazlman A Menon RK 《The Journal of biological chemistry》1999,274(48):34327-34336
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