Macrophage GIT1 promotes oligodendrocyte precursor cell differentiation and remyelination after spinal cord injury.
Glia
; 72(9): 1674-1692, 2024 09.
Article
in En
| MEDLINE
| ID: mdl-38899731
ABSTRACT
Spinal cord injury (SCI) can result in severe motor and sensory deficits, for which currently no effective cure exists. The pathological process underlying this injury is extremely complex and involves many cell types in the central nervous system. In this study, we have uncovered a novel function for macrophage G protein-coupled receptor kinase-interactor 1 (GIT1) in promoting remyelination and functional repair after SCI. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we identified that GIT1 deficiency in macrophages led to an increased generation of tumor necrosis factor-alpha (TNFα), reduced proportion of mature oligodendrocytes (mOLs), impaired remyelination, and compromised functional recovery in vivo. These effects in GIT1 CKO mice were reversed with the administration of soluble TNF inhibitor. Moreover, bone marrow transplantation from GIT1 CWT mice reversed adverse outcomes in GIT1 CKO mice, further indicating the role of macrophage GIT1 in modulating spinal cord injury repair. Our in vitro experiments showed that macrophage GIT1 plays a critical role in secreting TNFα and influences the differentiation of oligodendrocyte precursor cells (OPCs) after stimulation with myelin debris. Collectively, our data uncovered a new role of macrophage GIT1 in regulating the transformation of OPCs into mOLs, essential for functional remyelination after SCI, suggesting that macrophage GIT1 could be a promising treatment target of SCI.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spinal Cord Injuries
/
Cell Differentiation
/
Oligodendrocyte Precursor Cells
/
Remyelination
/
Macrophages
Limits:
Animals
Language:
En
Journal:
Glia
Journal subject:
NEUROLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China