SDS3 regulates microglial inflammation by modulating the expression of the upstream kinase ASK1 in the p38 MAPK signaling pathway.
Inflamm Res
; 73(9): 1547-1564, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39008037
ABSTRACT
BACKGROUND:
Microglia, the main innate immune cells in the central nervous system, are key drivers of neuroinflammation, which plays a crucial role in the pathogenesis of neurodegenerative diseases. The Sin3/histone deacetylase (HDAC) complex, a highly conserved multiprotein co-repressor complex, primarily performs transcriptional repression via deacetylase activity; however, the function of SDS3, which maintains the integrity of the complex, in microglia remains unclear.METHODS:
To uncover the regulatory role of the transcriptional co-repressor SDS3 in microglial inflammation, we used chromatin immunoprecipitation to identify SDS3 target genes and combined with transcriptomics and proteomics analysis to explore expression changes in cells following SDS3 knocking down. Subsequently, we validated our findings through experimental assays.RESULTS:
Our analysis revealed that SDS3 modulates the expression of the upstream kinase ASK1 of the p38 MAPK pathway, thus regulating the activation of signaling pathways and ultimately influencing inflammation.CONCLUSIONS:
Our findings provide important evidence of the contributions of SDS3 toward microglial inflammation and offer new insights into the regulatory mechanisms of microglial inflammatory responses.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Repressor Proteins
/
Microglia
/
MAP Kinase Kinase Kinase 5
/
P38 Mitogen-Activated Protein Kinases
/
Inflammation
Limits:
Animals
/
Humans
Language:
En
Journal:
Inflamm Res
/
Inflamm. res
/
Inflammation research
Journal subject:
ALERGIA E IMUNOLOGIA
/
PATOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China
Country of publication:
Switzerland