由ASH2L介导的H3K4me3通过HIPK2和Notch1通道驱动糖尿病病
Wen Zhong1, Chen Hong1, Yuyu Zhang1
1Pharmacophenomics Laboratory, Human Phenome Institute, Fudan University, Shanghai 201203, China.
概括
通过促进脏炎症和纤维化,ASH2L上调会加剧糖尿病病 (DN). 抑制ASH2L可以防止高血糖引起的损伤,为DN提供潜在的治疗标.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 糖尿病病 (DN) 是糖尿病的严重并发症,导致功能衰竭.
- 表观遗传因子ASH2L在DN病变发生中的作用,特别是它涉及H3K4me3的机制,仍然不清楚.
- 之前的研究表明,ASH2L在高葡萄糖条件下加剧纤维化和炎症.
研究的目的:
- 调查ASH2L介导的H3K4me3在糖尿病病中的病理生理学相关性和机制.
- 为了确定ASH2L在糖尿病脏的上调是否有助于球损伤.
- 探索针对ASH2L作为DN治疗策略的潜力.
主要方法:
- 使用db/db小鼠作为糖尿病病的模型.
- 评估了球损伤标志物,包括白膜尿,脏结构和细胞外基质沉积.
- 分析了ASH2L,H3K4me3,ADAM17,HIPK2和Notch1信号通路组件的表达.
主要成果:
- 在db/db小鼠的淋巴细胞中发现ASH2L被上调.
- 失去了ASH2L,显著地保护免受高血糖引起的球损伤,减少纤维化和炎症.
- 在ADAM17和HIPK2促进体上通过ASH2L介导的H3K4me3丰富激活了它们的转录,异常的Notch1信号,并导致DN病理.
结论:
- ASH2L在糖尿病病的发展和进展中起着至关重要的作用.
- 针对ASH2L及其下游信号通路,为DN治疗提供了一个有前途的治疗途径.
- 了解ASH2L-H3K4me3-Notch1轴为DN病原发生提供了新的见解.
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