| 摘要: |
| 常染色体显性遗传性多囊肾病(ADPKD)是一种常见的遗传性疾病,发病率约为1/1 000～1/400。ADPKD中基因表达的表观遗传修饰和蛋白质功能的研究已成为最近研究的热点。表观遗传乙酰化修饰中的组蛋白去乙酰化酶(HDACs)参与调节了Pkd1基因的表达,其中HDAC5是液体流动引起的肾上皮细胞钙信号通路作用的靶点；HDAC6在囊泡表皮细胞中过度表达,通过α-tubulin去乙酰化参与调节纤毛形成和表皮生长因子受体（EGFR）的运输,并且通过β-catenin去乙酰化调节Wnt信号通路。HDAC抑制剂既能减少Pkd1基因条件性敲除小鼠囊肿的形成,又能延缓Pkd2基因敲除小鼠肾功能下降,因此抑制HDAC可能成为治疗ADPKD的新靶点。本文主要就ADPKD去乙酰化修饰方面的研究作一综述。 |
| 关键词: 常染色体显性多囊肾 组蛋白脱乙酰基酶类 表观遗传 |
| DOI：10.3724/SP.J.1008.2011.0663 |
| 投稿时间：2010-11-11修订日期：2010-12-15 |
| 基金项目: |
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| Histone deacetylases and autosomal dominant polycystic kidney disease |
| XUE Cheng,MEI Chang-lin* |
| (Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai 200003,China) |
| Abstract: |
| Autosomal dominant polycystic kidney disease(ADPKD)is the most frequent inherited kidney disease，the incidence rate is about 100-250 per 100,000．The roles of epigenetic modulation of gene expression and protein functions in ADPKD have recently become the focus of scientific investigation.Evidence generated to-date indicates that one of the epigenetic modifiers, histone deacetylases (HDACs),are important regulators of ADPKD. HDACs are involved in regulating the expression of the Pkd1 gene and are the target of fluid flow-induced calcium signal in kidney epithelial cells.The expression of HDAC6 is upregulated in cystic epithelial cells.HDAC6 can regulate ciliogenesis and epidermal growth factor receptor(EGFR) trafficking through deacetylating α-tubulin and regulate Wnt signaling through deacetylating β-catenin. HDAC inhibitors have been found to reduce the progression of cyst formation and slow the decline of kidney function in Pkd1 conditional knockout mice and Pkd2 knockout mice, respectively,implicating the potential clinical application of HDAC inhibitors on ADPKD. |
| Key words: polycystic kidney disease,autosomal dominant, histone deacetylase,epigenetics |
