UBE2I介导VDR类泛素化修饰降低炎症性肠病炎性小体活化保护肠道微环境平衡

控制炎症性肠病（IBD）复发、维持长期缓解是目前难题，而提高肠道保护和修复方面的基础研究尚欠缺。维生素D受体（VDR）是促进肠黏膜保护的关键转录因子，其活性受到多层面调控，进而影响维生素D(VitD)对VDR的激活效应，导致VitD/VDR轴异常。本课题组前期工作提示VDR受到多个非编码RNA调控，可维持IBD黏膜屏障功能，并可能有调节细胞焦亡的功能。本研究利用蛋白质修饰组学技术从蛋白翻译后水平探究VDR蛋白修饰调控，提出假设:1）非编码RNA、蛋白修饰立体网络调控IBD中VDR转录活性，其中类泛素化（SUMO）化修饰显著抑制VDR转录活性，并由UBE2I/UBC介导。2）抑制IBD细胞凋亡中炎性小体活性是VDR炎症和免疫调节中的新功能，SUMO化修饰可调控影响VDR新功能。期望通过本研究获得VDR转录调控的立体精细化网络和关键点, 挖掘VDR新功能及IBD保护机制的关键靶点。

Abstract：Preventing relapse and maintaining remission is a difficult problem in the treatment of inflammatory bowel disease(IBD). Very few studies reported the protection or restoration mechanisms of intestinal mucosa. Vitamin D receptor(VDR)is a vital transcription factor in inducing intestinal mucosa protection. Multiple pathways modulate the activity of VDR and influence its response to vitamin D. Our previous studies showed that VDR was regulated by multiple non-coding RNAs. Furthermore，VDR was beneficial in maintenance of intestinal barrier function and regulation of celluar pyroptosis.Based on advancement in proteomics modification, this research is focused on how VDR modifies protein in the process of post-translation modification.Our project aims at： 1）A network of non-coding RNA and protein modification regulates the transcriptional activity of VDR, and UBE21/UBC-mediated sumolyation decreases the transcriptional activity of VDR.2）Inflammasome,whose activity is regulated by VDR, inhibits cellular pyroptosis in IBD. Sumolyation influences the regulatory function of VDR. The research purposes are to establish the network and figure out core section in the regulation of VDR transcription, to define the key part among protective mechanisms in the network of IBD inflammation and immunity modulation，and to open up broad prospects of VDR in clinical application.