HuR deficiency abrogated the enhanced NLRP3 signaling in experimental ischemic stroke.
FASEB J
; 38(1): e23342, 2024 01.
Article
en En
| MEDLINE
| ID: mdl-38038724
ABSTRACT
Human antigen R (HuR) is a universally expressed RNA-binding protein that plays an essential role in governing the fate of mRNA transcripts. Accumulating evidence indicated that HuR is involved in the development and functions of several cell types. However, its role in cerebral ischemia/reperfusion injury (CIRI) remains unclear. In this study, we found that HuR was significantly upregulated after CIRI. Moreover, we found that silencing HuR could inhibit the inflammatory response of microglia and reduce the damage to neurons caused by oxygen-glucose deprivation/reperfusion treatment. In vivo, we found that microglial HuR deficiency significantly ameliorated CIRI and reduced NLRP3-mediated inflammasome activation. Mechanistically, we found that HuR could regulate NLRP3 mRNA stability by binding to the AU-rich element (ARE) region within the 3' untranslated region (UTR) of NLRP3 mRNA. In addition, we found that the upregulation of HuR was dependent on the upregulation of NADPH oxidase-mediated ROS accumulation. Collectively, our studies revealed that HuR could regulate NLRP3 expression and that HuR deficiency abrogated the enhanced NLRP3 signaling in experimental ischemic stroke. Targeting HuR may be a novel therapeutic strategy for cerebral ischemic stroke treatment.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Daño por Reperfusión
/
Isquemia Encefálica
/
Accidente Cerebrovascular Isquémico
Límite:
Animals
Idioma:
En
Revista:
FASEB J
/
FASEB j
/
FASEB journal
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China