课题基金基金详情
细胞因子诱导的SH2结构包含蛋白(CISH)调控肠道炎症和代谢的作用与机制
结题报告
批准号:
81970731
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
胡小明
依托单位:
学科分类:
能量代谢调节异常与肥胖
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
胡小明
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中文摘要
肠道作为分泌和代谢器官,对代谢稳态发挥关键作用,但具体调控机制仍需阐明。CISH属于SOCS蛋白家族成员之一,主要作为细胞因子信号抑制子起作用。我们前期工作发现人群和小鼠肠炎模型中,CISH在肠道中表达显著下调;且发现亮氨酸缺乏改变小鼠代谢模型中,肠道CISH表达显著升高。这些结果提示,肠道CISH可能对机体代谢有重要调控功能。进一步构建了肠上皮细胞特异敲除Cish的小鼠模型,发现该小鼠体温下降和血糖升高的代谢表型。因此,我们提出假设:肠道CISH在炎症中具有关键作用,且其介导的肠道信号改变对糖脂代谢发挥重要作用。本项目拟利用肠道敲除Cish小鼠及细胞模型,结合iTRAQ定量蛋白质组学、16S rDNA测序等技术深入分析肠道CISH调控信号及菌群的作用,阐明它们介导肠道CISH影响炎症/糖脂代谢的作用及机制。这将加深人们对肠道CISH调控代谢的认识,有助于开发靶向肠道治疗代谢疾病的新药物。
英文摘要
Intestinal tract is a secretory and metabolic organ, plays a key role in the homeostasis of glucose and lipid metabolism, but the regulatory mechanism still needs to be clarified. CISH is one of the members of the SOCS protein family and plays an important role as a cytokine signal suppressor. We previously found that the expression of CISH was significantly decreased in intestinal mucosa of patients with inflammatory bowel disease and colonic epithelial cells of mice with DSS-induced colitis, suggesting that CISH plays an important role in intestinal inflammation. Interestingly, we found that Cish expression was significant increased by leucine deprivation, and then constructed a mouse model of intestinal epithelial cell-specific knockout of Cish and found that these mice have the metabolic phenotypes of decreasing body temperature and increasing blood glucose. Based on these, we hypothesize that intestinal CISH plays a key role in inflammation, and the intestinal signal changes mediated by CISH play an important role in whole glucose and lipid metabolism. This project will use intestinal knockout Cish mice and cell models, and combine with iTRAQ quantitative proteomics and bacterial 16S rDNA sequencing technologies to explore the key signaling pathways and gut microbiota regulated by intestinal CISH, and further clarify the role and mechanism of intestinal CISH in inflammation, glucose and lipid metabolism. This study will deepen people's understanding of intestinal CISH regulation of metabolism, and help to develop new drugs targeting intestinal signals for obesity and metabolic diseases.
期刊论文列表
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科研奖励列表
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专利列表
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DOI:10.1038/s42003-022-03609-0
发表时间:2022-07-01
期刊:Communications biology
影响因子:5.9
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AgRP 神经元中 c-Jun 的抑制会增加应激引起的焦虑和结肠炎易感性。
DOI:10.1038/s42003-023-04425-w
发表时间:2023-01-14
期刊:COMMUNICATIONS BIOLOGY
影响因子:5.9
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Hepatic cytokine-inducible SH2-containing protein (CISH) regulates gluconeogenesis via cAMP-responsive element binding protein (CREB)
肝细胞因子诱导的 SH2 蛋白 (CISH) 通过 cAMP 反应元件结合蛋白 (CREB) 调节糖异生
DOI:10.1096/fj.202200870r
发表时间:2022-10-01
期刊:FASEB JOURNAL
影响因子:4.8
作者:Xiao,Fei;Deng,Jiali;Guo,Feifan
通讯作者:Guo,Feifan
DOI:doi: 10.1093/ecco-jcc/jjad041.
发表时间:2023
期刊:Journal of Crohn’s and Colitis
影响因子:--
作者:Xiaoming Hu;Fuxin Jiao;Jiali Deng;Ziheng Zhou;Shanghai Chen;Changqin Liu;Zhanju Liu;Feifan Guo
通讯作者:Feifan Guo
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肝因子 ERAP1 通过抑制 USP33 介导的 ADRB2 去泛素化扰乱骨骼肌胰岛素敏感性。
DOI:10.2337/db21-0857
发表时间:2022
期刊:Diabetes
影响因子:7.7
作者:Yuguo Niu;Haizhou Jiang;Hanrui Yin;Fenfen Wang;Ronggui Hu;Xiaoming Hu;B. Peng;Yousheng Shu;Zhigang Li;Shanghai Chen;Feifan Guo
通讯作者:Feifan Guo
国内基金
海外基金