A novel RIP1/RIP3 dual inhibitor promoted OPC survival and myelination in a rat neonatal white matter injury model with hOPC graft.
A novel RIP1/RIP3 dual inhibitor promoted OPC survival and myelination in a rat neonatal white matter injury model with hOPC graft.
复制标题
新型 RIP1/RIP3 双抑制剂促进 hOPC 移植大鼠新生白质损伤模型中的 OPC 存活和髓鞘形成
DOI：
10.1186/s13287-021-02532-1
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发表时间：
2021-08-18
影响因子：
7.5
通讯作者：
Yao R
中科院分区：
文献类型：
--
作者：
Zhang C;Guan Q;Shi H;Cao L;Liu J;Gao Z;Zhu W;Yang Y;Luan Z;Yao R
BackgroundThe dual inhibitors of receptor interacting protein kinase-1 and -3 (RIP1 and RIP3) play an important role in cell death processes and inflammatory responses. White matter injury (WMI), a leading cause of neurodevelopmental disabilities in preterm infants, which is characterized by extensive myelination disturbances and demyelination. Neuroinflammation, leads to the loss and differentiation-inhibition of oligodendrocyte precursor cells (OPCs), represents a major barrier to myelin repair. Whether the novel RIP1/RIP3 dual inhibitor ZJU-37 can promote transplanted OPCs derived from human neural stem cells (hOPCs) survival, differentiation and myelination remains unclear. In this study, we investigated the effect of ZJU-37 on myelination and neurobehavioral function in a neonatal rat WMI model induced by hypoxia and ischemia.MethodsIn vivo, P3 rat pups were subjected to right common carotid artery ligation and hypoxia, and then treated with ZJU-37 or/and hOPCs, then OPCs apoptosis, myelination, glial cell and NLRP3 inflammasome activation together with cognitive outcome were evaluated at 12 weeks after transplantation. In vitro, the effect of ZJU-37 on NLRP3 inflammasome activation in astrocytes induced by oxygen–glucose deprivation (OGD) were examined by western blot and immunofluorescence. The effect of ZJU-37 on OPCs apoptosis induced by the conditioned medium from OGD-injured astrocytes (OGD-astrocyte-CM) was analyzed by flow cytometry and immunofluorescence.ResultsZJU-37 combined with hOPCs more effectively decreased OPC apoptosis, promoted myelination in the corpus callosum and improved behavioral function compared to ZJU-37 or hOPCs treatment. In addition, the activation of glial cells and NLRP3 inflammasome was reduced by ZJU-37 or/and hOPCs treatment in the neonatal rat WMI model. In vitro, it was also confirmed that ZJU-37 can suppress NLRP3 inflammasome activation in astrocytes induced by OGD. Not only that, the OGD-astrocyte-CM treated with ZJU-37 obviously attenuated OPC apoptosis and dysdifferentiation caused by the OGD-astrocyte-CM.ConclusionsThe novel RIP1/RIP3 dual inhibitor ZJU-37 may promote OPC survival, differentiation and myelination by inhibiting NLRP3 inflammasome activation in a neonatal rat model of WMI with hOPC graft.
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影响因子：
23.9
作者：
Li L;Tian E;Chen X;Chao J;Klein J;Qu Q;Sun G;Sun G;Huang Y;Warden CD;Ye P;Feng L;Li X;Cui Q;Sultan A;Douvaras P;Fossati V;Sanjana NE;Riggs AD;Shi Y
通讯作者：
Shi Y
影响因子：
6
作者：
Manley NC;Priest CA;Denham J;Wirth ED 3rd;Lebkowski JS
通讯作者：
Lebkowski JS
影响因子：
3.3
作者：
Kim TK;Park D;Ban YH;Cha Y;An ES;Choi J;Choi EK;Kim YB
通讯作者：
Kim YB
影响因子：
3.6
作者：
Messerschmidt, Agnes;Fuiko, Renate;Birnbacher, Robert
通讯作者：
Birnbacher, Robert
移植的过表达 miR-219 的少突胶质细胞前体细胞促进慢性脱髓鞘模型的髓鞘再生并改善功能恢复
影响因子：
4.6
作者：
Fan HB;Chen LX;Qu XB;Ren CL;Wu XX;Dong FX;Zhang BL;Gao DS;Yao RQ
通讯作者：
Yao RQ