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Beyond knockout A novel homodimerization-targeting MyD88 inhibitor prevents and cures type 1 diabetes in NOD mice

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收录情况： ◇ SCIE

作者：
Zhang,Xue[1] * ; Xing,Shuai[1] ; Li,Mingqiang[1] ; Zhang,Limin[1] ; Xie,Lin[1] ; He,Wentao[6] ; Liu,Jianhua[1] ; Chang,Sheng[1] ; Jiang,Fengchao[7,*1] ; Zhou,Ping[1,3,*1] ;
单位： [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Organ Transplantat, Wuhan 430030, Peoples R China [2]Minist Hlth, Key Lab Organ Transplantat, Wuhan, Peoples R China [3]Minist Educ, Key Lab Organ Transplantat, 1095 Jiefang Ave, Wuhan 430030, Hubei Province, Peoples R China [4]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Gastroenterol, Wuhan 430030, Peoples R China [5]Taian City Cent Hosp, Dept Surg, Tai An 271000, Shandong, Peoples R China [6]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Endocrinol, Wuhan 430030, Peoples R China [7]Huazhong Univ Sci & Technol, Tongji Med Coll, Acad Pharmacol, Wuhan 430030, Peoples R China
出处：
DOI： 10.1016/j.metabol.2016.05.005
ISSN：

关键词： Type 1 diabetes Therapeutics MyD88 MyD88 inhibitor DC

摘要：
Introduction and aims. Studies have reported that myeloid differentiation factor 88 (MyD88) plays an important role in the development of type 1 diabetes (T1D). The aim of this study was to determine the effects of the self-created MyD88 inhibitor, TJ-M2010-6, in preventing and treating T1D. Methods. Molecule docking and co-immunoprecipitation were used to determine the suppressing capability of TJ-M2010-6 on the homodimerization of MyD88. The preventive and therapeutic effects of TJ-M2010-6 were tested in NOD mice. Results. TJ-M2010-6 interacted with amino acid residues of the MyD88 TIR domain and inhibited MyD88 homodimerization. Continuous administration of TJ-M2010-6 significantly reduced the onset of diabetes during the observation period in NOD mice (36.4% vs. 80%, P < 0.01). Although the immediate TJ-M2010-6 treatment group showed a retardation in the rise of their blood glucose level, the delayed treatment group did not show this effect. Mechanism studies have shown that TJ-M2010-6 treatment significantly inhibits insulitis in vivo. In vitro, TJ-M2010-6 inhibited the maturation of DCs, leading to the suppression of T cell activation and inflammatory cytokine secretion. Conclusions. These results demonstrated that the strategy targeted at the innate immune system using the MyD88 inhibitor had a profound significance in preventing and treating T1D. (C) 2016 Elsevier Inc. All rights reserved.

基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81072442, 81102260, 81471588]; Special Project of Ministry of Health [201302009]; National Hightech Researching and Developing Program (Program 863) of Ministry of Science and Technology of ChinaNational High Technology Research and Development Program of China [2012AA021010]
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外文
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中科院(CAS)分区：
出版当年[2015]版：
大类 | 2 区 医学
小类 | 3 区 内分泌学与代谢
最新[2025]版：
大类 | 1 区 医学
小类 | 1 区 内分泌学与代谢
JCR分区：
出版当年[2014]版：
Q2 ENDOCRINOLOGY & METABOLISM
最新[2024]版：
Q1 ENDOCRINOLOGY & METABOLISM

影响因子： 最新[2024版] 最新五年平均 出版当年[2014版] 出版当年五年平均 出版前一年[2013版] 出版后一年[2015版]

第一作者：
第一作者单位： [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Organ Transplantat, Wuhan 430030, Peoples R China
通讯作者：
通讯机构： [1]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Inst Organ Transplantat, Wuhan 430030, Peoples R China [3]Minist Educ, Key Lab Organ Transplantat, 1095 Jiefang Ave, Wuhan 430030, Hubei Province, Peoples R China [7]Huazhong Univ Sci & Technol, Tongji Med Coll, Acad Pharmacol, Wuhan 430030, Peoples R China [*1]Huazhong Univ Sci & Technol, Tongji Hosp, Inst Organ Transplantat, Key Lab Organ Transplantat,Minist Hlth, 1095 Jiefang Ave, Wuhan 430030, Hubei Province, Peoples R China
推荐引用方式(GB/T 7714)：
Zhang Xue,Xing Shuai,Li Mingqiang,et al.Beyond knockout A novel homodimerization-targeting MyD88 inhibitor prevents and cures type 1 diabetes in NOD mice[J].METABOLISM-CLINICAL AND EXPERIMENTAL.2016,65(9):1267-1277.doi:10.1016/j.metabol.2016.05.005.
APA：
Zhang,Xue,Xing,Shuai,Li,Mingqiang,Zhang,Limin,Xie,Lin...&Zhou,Ping.(2016).Beyond knockout A novel homodimerization-targeting MyD88 inhibitor prevents and cures type 1 diabetes in NOD mice.METABOLISM-CLINICAL AND EXPERIMENTAL,65,(9)
MLA：
Zhang,Xue,et al."Beyond knockout A novel homodimerization-targeting MyD88 inhibitor prevents and cures type 1 diabetes in NOD mice".METABOLISM-CLINICAL AND EXPERIMENTAL 65..9(2016):1267-1277

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