Lipocalin-2-Mediated Insufficient Oligodendrocyte Progenitor Cell Remyelination for White Matter Injury After Subarachnoid Hemorrhage via SCL22A17 Receptor/Early Growth Response Protein 1 Signaling.
10.1007/s12264-022-00906-w
- Author:
Qiang LI
1
;
Xufang RU
1
;
Yang YANG
1
;
Hengli ZHAO
1
;
Jie QU
1
;
Weixiang CHEN
1
;
Pengyu PAN
1
;
Huaizhen RUAN
2
;
Chaojun LI
3
;
Yujie CHEN
4
;
Hua FENG
1
Author Information
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. licj@nju.edu.cn.
4. 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. yujiechen6886@foxmail.com.
- Publication Type:Journal Article
- Keywords:
Early growth response protein 1;
Lipocalin-2;
Multiple sclerosis;
Oligodendrocyte progenitor cell;
Remyelination;
Subarachnoid hemorrhage;
White matter injury
- MeSH:
Mice;
Animals;
Remyelination/physiology*;
Oligodendrocyte Precursor Cells/metabolism*;
White Matter;
Subarachnoid Hemorrhage/metabolism*;
Lipocalin-2/metabolism*;
Early Growth Response Protein 1/metabolism*;
Oligodendroglia/metabolism*;
Mice, Knockout;
Cell Differentiation/physiology*;
Brain Injuries/metabolism*
- From:
Neuroscience Bulletin
2022;38(12):1457-1475
- CountryChina
- Language:English
-
Abstract:
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.
