TMAO Promotes NLRP3 Inflammasome Activation of Microglia Aggravating Neurological Injury in Ischemic Stroke Through FTO/IGF2BP2.
J Inflamm Res
; 16: 3699-3714, 2023.
Article
em En
| MEDLINE
| ID: mdl-37663757
ABSTRACT
Objective:
Stroke is a kind of cerebrovascular disease with high mortality. TMAO has been shown to aggravate stroke outcomes, but its mechanism remains unclear. Materials andMethods:
Mice were fed with 0.12% TMAO for 16 weeks. Then, mice were made into MCAO/R models. Neurological score, infarct volume, neuronal damage and markers associated with inflammation were assessed. Since microglia played a crucial role in ischemic stroke, microglia of MCAO/R mice were isolated for high-throughput sequencing to identify the most differentially expressed gene following TMAO treatment. Afterward, the downstream pathways of TMAO were investigated using primary microglia.Results:
TMAO promoted the release of inflammatory cytokines in the brain of MCAO/R mice and promoted the activation of OGD/R microglial inflammasome, thereby exacerbating ischemic stroke outcomes. FTO/IGF2BP2 inhibited NLRP3 inflammasome activation in OGD/R microglia by downregulating the m6A level of NLRP3. TMAO can inhibit the expression of FTO and IGF2BP2, thus promoting the activation of NLRP3 inflammasome in OGD/R microglia. In conclusion, these results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2.Conclusion:
Our results demonstrated that TMAO promotes NLRP3 inflammasome activation of microglia aggravating neurological injury in ischemic stroke through FTO/IGF2BP2. These findings explained the molecular mechanism of TMAO aggravating ischemic stroke in detail and provided molecular mechanism for clinical treatment.
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Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article