Lipocalin-2-Mediated Insufficient Oligodendrocyte Progenitor Cell Remyelination for White Matter Injury After Subarachnoid Hemorrhage via SCL22A17 Receptor/Early Growth Response Protein 1 Signaling.
Qiang LiXufang RuYang YangHengli ZhaoJie QuWeixiang ChenPengyu PanHuaizhen RuanChaojun LiYu-Jie ChenHua FengPublished in: Neuroscience bulletin (2022)
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.
Keyphrases
- white matter
- subarachnoid hemorrhage
- multiple sclerosis
- cerebral ischemia
- brain injury
- transcription factor
- binding protein
- single cell
- traumatic brain injury
- gene expression
- protein protein
- cell therapy
- poor prognosis
- blood brain barrier
- intensive care unit
- genome wide
- amino acid
- rna seq
- dna methylation
- hepatitis b virus
- mechanical ventilation
- acute respiratory distress syndrome