Lipocalin-2-Mediated Insufficient Oligodendrocyte Progenitor Cell Remyelination for White Matter Injury After Subarachnoid Hemorrhage via SCL22A17 Receptor/Early Growth Response Protein 1 Signaling  

作　　者：Qiang Li Xufang Ru Yang Yang Hengli Zhao Jie Qu Weixiang Chen Pengyu Pan Huaizhen Ruan Chaojun Li Yujie Chen Hua Feng 

机构地区：[1]Department of Neurosurgery and State Key Laboratory of Trauma,Burn and Combined Injury,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China [2]Department of Neurobiology,College of Basic Medical Sciences,Third Military Medical University(Army Medical University),Chongqing 400038,China [3]Model Animal Research Center,Nanjing University,Nanjing 210032,China [4]Chongqing Key Laboratory of Precision Neuromedicine and Neuroregenaration,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China [5]Chongqing Clinical Research Center for Neurosurgery,Southwest Hospital,Third Military Medical University(Army Medical University),Chongqing 400038,China

出　　处：《Neuroscience Bulletin》2022年第12期1457-1475,共19页神经科学通报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(81901216 and 82030036);Southwest Hospital(SWH2018BJKJ-05 and SWH2015QN13);the Chongqing Talent Program(4139Z2391).

摘　　要：Insufficient remyelination due to impaired oligodendrocyte precursor cell(OPC)differentiation and maturation is strongly associated with irreversible white matter injury(WMI)and neurological deficits.We analyzed whole transcriptome expression to elucidate the potential role and underlying mechanism of action of lipocalin-2(LCN2)in OPC differentiation and WMI and identified the receptor SCL22A17 and downstream transcription factor early growth response protein 1(EGR1)as the key signals contributing to LCN2-mediated insufficient OPC remyelination.In LCN-knockdown and OPC EGR1 conditional-knockout mice,we discovered enhanced OPC differentiation in developing and injured white matter(WM);consistent with this,the specific inactivation of LCN2/SCl22A17/EGR1 signaling promoted remyelination and neurological recovery in both atypical,acute WMI due to subarachnoid hemorrhage and typical,chronic WMI due to multiple sclerosis.This potentially represents a novel strategy to enhance differentiation and remyelination in patients with white matter injury.

关 键 词：White matter injury Oligodendrocyte progenitor cell REMYELINATION Subarachnoid hemorrhage Multiple sclerosis Lipocalin-2 Early growth response protein 1 

分 类 号：R744.5[医药卫生—神经病学与精神病学]