Lipocalin-2-Mediated Insufficient Oligodendrocyte Progenitor Cell Remyelination for White Matter Injury After Subarachnoid Hemorrhage via SCL22A17 Receptor/Early Growth Response Protein 1 Signaling.
Lipocalin-2-Mediated Insufficient Oligodendrocyte Progenitor Cell Remyelination for White Matter Injury After Subarachnoid Hemorrhage via SCL22A17 Receptor/Early Growth Response Protein 1 Signaling.
复制标题
Lipocalin-2 通过 SCL22A17 受体/早期生长反应蛋白 1 信号转导介导少突胶质细胞祖细胞髓鞘再生不足导致蛛网膜下腔出血后白质损伤
DOI：
10.1007/s12264-022-00906-w
复制
发表时间：
2022-12
影响因子：
5.6
通讯作者：
Feng, Hua
中科院分区：
文献类型：
--
作者：
Li, Qiang;Ru, Xufang;Yang, Yang;Zhao, Hengli;Qu, Jie;Chen, Weixiang;Pan, Pengyu;Ruan, Huaizhen;Li, Chaojun;Chen, Yujie;Feng, Hua
关键词：
由于少突胶质前体细胞（OPC）分化和成熟受损导致的髓鞘再生不足与不可逆的白色损伤（白质损伤）和神经功能缺损密切相关。我们分析了整个转录组表达，以阐明脂质运载蛋白-2（LCN 2）在OPC分化和脱髓鞘中的潜在作用和潜在作用机制，并确定受体SCL 22 A17和下游转录因子早期生长反应蛋白1（EGR 1）是导致LCN 2介导的OPC髓鞘再生不足的关键信号。在LCN敲除和OPC EGR 1条件敲除小鼠中，我们发现在发育和受损的白色物质（WM）中OPC分化增强;与此一致，LCN 2/SCl 22 A17/EGR 1信号传导的特异性失活促进了蛛网膜下腔出血所致的非典型急性脑脊髓损伤和多发性硬化所致的典型慢性脑脊髓损伤的髓鞘再生和神经恢复。这可能代表了一种新的策略，以提高分化和髓鞘再生患者的白色物质损伤。在线版本包含补充材料，可通过10.1007/s12264-022-00906-w获得。
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. The online version contains supplementary material available at 10.1007/s12264-022-00906-w.
登录
查看更多内容
影响因子：
5.8
作者：
Bhusal, Anup;Rahman, Md Habibur;Suk, Kyoungho
通讯作者：
Suk, Kyoungho
影响因子：
5.8
作者：
Khalil, M.;Renner, A.;Fazekas, F.
通讯作者：
Fazekas, F.
影响因子：
158.5
作者：
Chang, A;Tourtellotte, WW;Trapp, BD
通讯作者：
Trapp, BD
影响因子：
1.3
作者：
Lee, Shinrye;Jha, Mithilesh Kumar;Suk, Kyoungho
通讯作者：
Suk, Kyoungho
影响因子：
11
作者：
Kang SS;Ren Y;Liu CC;Kurti A;Baker KE;Bu G;Asmann Y;Fryer JD
通讯作者：
Fryer JD