The RNA m6A modification might participate in microglial activation during hypoxic-ischemic brain damage in neonatal mice.
Hum Genomics
; 17(1): 78, 2023 08 25.
Article
en En
| MEDLINE
| ID: mdl-37626401
ABSTRACT
BACKGROUND:
The RNA m6A modification has been implicated in multiple neurological diseases as well as macrophage activation. However, whether it regulates microglial activation during hypoxic-ischemic brain damage (HIBD) in neonates remains unknown. Here, we aim to examine whether the m6A modification is involved in modulating microglial activation during HIBD. We employed an oxygen and glucose deprivation microglial model for in vitro studies and a neonatal mouse model of HIBD. The brain tissue was subjected to RNA-seq to screen for significant changes in the mRNA m6A regulator. Thereafter, we performed validation and bioinformatics analysis of the major m6A regulators.RESULTS:
RNA-seq analysis revealed that, among 141 m6A regulators, 31 exhibited significant differential expression (FC (abs) ≥ 2) in HIBD mice. We then subjected the major m6A regulators Mettl3, Mettl14, Fto, Alkbh5, Ythdf1, and Ythdf2 to further validation, and the results showed that all were significantly downregulated in vitro and in vivo. GO analysis reveals that regulators are mainly involved in the regulation of cellular and metabolic processes. The KEGG results indicate the involvement of the signal transduction pathway.CONCLUSIONS:
Our findings demonstrate that m6A modification of mRNA plays a crucial role in the regulation of microglial activation in HIBD, with m6A-associated regulators acting as key modulators of microglial activation.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Microglía
/
Activación de Macrófagos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Hum Genomics
Asunto de la revista:
GENETICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China