OASIS, a CREB/ATF-family transcription factor, modulate transcription of C6ST1 gene and chondroitin sulfation

OASIS 是一种 CREB/ATF 家族转录因子，调节 C6ST1 基因的转录和软骨素硫酸化

• 批准号: 22791353
• 负责人: OKUDA Hiroaki
• 金额: $ 2.58万
• 依托单位: Nara Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22791353/
• 关键词: アストロサイト

In the central nerve system, ER stress is implicated in a wide range of disorders including ischemic injury and neurodegenerative disorder. Both mRNA and protein levels of OASIS were elevated in the injured cortex and correlated closely with those of reactive astrocyte. Reactive astrocyte, which constitute a major cellular component of glial scar, enmesh the lesion site and produce anti-regenerative molecules such as chondroitin sulphate proteoglycans(CSPGs). We have analyzed the mRNA levels of the CS-glycosaminoglycan synthesizing enzymes using OASIS knockout mice. Expression of chondroitin 6-sulfotransferase 1(C6ST1) is increased in cortical stub injury in wild type mice, but is not in OASIS knock out mice. Furthermore, OASIS bound to the first intron region and promoted transcription of C6ST1.These results suggest that OASIS may be involved in CSPG production through the transcription of C6ST1 in astrocytes.

在中枢神经系统中，内质网应激与多种疾病有关，包括缺血性损伤和神经退行性疾病。损伤皮质中 OASIS 的 mRNA 和蛋白水平均升高，并与反应性星形胶质细胞密切相关。反应性星形胶质细胞是神经胶质疤痕的主要细胞成分，它会侵入病变部位并产生抗再生分子，例如硫酸软骨素蛋白聚糖（CSPG）。我们使用 OASIS 基因敲除小鼠分析了 CS-糖胺聚糖合成酶的 mRNA 水平。在野生型小鼠的皮质残端损伤中，软骨素 6-磺基转移酶 1 (C6ST1) 的表达增加，但在 OASIS 敲除小鼠中则没有增加。此外，OASIS与第一内含子区域结合并促进C6ST1的转录。这些结果表明OASIS可能通过星形胶质细胞中C6ST1的转录参与CSPG的产生。