单位：[1]Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Health, and Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan 430030, China.华中科技大学同济医学院附属同济医院器官移植研究所器官移植[2]Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University,Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan 430071, China.[3]The Central Hospital of Taian, Taian 271000, China.[4]Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.内科学系内分泌内科[5]Academy of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
The activation of innate immunity via myeloid differentiation factor 88 (MyD88) contributes to ischemia reperfusion (I/R) induced acute kidney injury (AKI) and chronic kidney injury. However, since there have not yet been any effective therapy, the exact pharmacological role of MyD88 in the prevention and treatment of renal ischemia reperfusion injury (IRI) is not known. We designed a small molecular compound, TJ-M2010-2, which inhibited MyD88 homodimerization. We used an established unilateral I/R mouse model. All mice undergoing 80 min ischemia through uninephrectomy died within five days without intervention. However, treatment with TJ-M2010-2 alone significantly improved the survival rate to 58.3%. Co-treatment of TJ-M2010-2 with the CD154 antagonist increased survival rates up to 100%. Twenty-eight days post-I/R of 60 min ischemia without nephrectomy, TJ-M2010-2 markedly attenuated renal interstitial and inhibited TGF-beta 1-induced epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. Furthermore, TJ-M2010-2 remarkably inhibited TLR/MyD88 signaling in vivo and in vitro. In conclusion, our findings highlight the promising clinical potential of MyD88 inhibitor in preventing and treating acute or chronic renal I/R injuries, and the therapeutic functionality of dual-system inhibition strategy in IRI-induced AKI. Moreover, MyD88 inhibition ameliorates renal I/R injury-induced tubular interstitial fibrosis by suppressing EMT.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81072442, 81471588, 81200498]; 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]; Special Project of Ministry of Health [201302009]
第一作者单位：[1]Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Health, and Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan 430030, China.
共同第一作者：
通讯作者：
通讯机构：[1]Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation, Ministry of Health, and Key Laboratory of Organ Transplantation, Ministry of Education, Wuhan 430030, China.[2]Institute of Hepatobiliary Diseases of Wuhan University, Zhongnan Hospital of Wuhan University,Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan 430071, China.[3]The Central Hospital of Taian, Taian 271000, China.
推荐引用方式(GB/T 7714)：
zhang li-min,liu jian-hua,xue cheng-biao,et al.Pharmacological inhibition of MyD88 homodimerization counteracts renal ischemia reperfusion-induced progressive renal injury in vivo and in vitro[J].SCIENTIFIC REPORTS.2016,6:doi:10.1038/srep26954.
APA：
zhang,li-min,liu,jian-hua,xue,cheng-biao,li,ming-qiang,xing,shuai...&zhou,ping.(2016).Pharmacological inhibition of MyD88 homodimerization counteracts renal ischemia reperfusion-induced progressive renal injury in vivo and in vitro.SCIENTIFIC REPORTS,6,
MLA：
zhang,li-min,et al."Pharmacological inhibition of MyD88 homodimerization counteracts renal ischemia reperfusion-induced progressive renal injury in vivo and in vitro".SCIENTIFIC REPORTS 6.(2016)
