NLRP3/miR-223-3p axis attenuates neuroinflammation induced by chronic intermittent hypoxia

© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature..

Obstructive sleep apnea (OSA) is mainly characterized by chronic intermittent hypoxia (CIH) with multiple brain injuries. Nucleotide oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome is considered the most important factor inducing and maintaining inflammation. However, the role of NLRP3 and its underlying mechanism in CIH-elicited neuroinflammation remains unclear. We constructed an OSA-related CIH in vivo model and assessed the rats' cognitive behavior in the Morris water maze. The combination of miR-223-3p and NLRP3 was confirmed by the TargetScan database, double luciferase reporter gene experiment, and RNA immunoprecipitation (RIP) experiment. Western blot and ELISA assay were used to analyze the effects of miR-223-3p targeting NLRP3 on the expression of pyroptotic or inflammatory factors in vivo in CIH rats. Severe cognitive impairment was observed in rats at week 6 post-treatment, with increased inflammatory factors in the blood and hippocampus, heightened NLRP3 expression, and low miR-223-3p levels. And the good binding activity of the two was confirmed by dual luciferase reporter and RIP experiments. Next, we found that silencing NLRP3 or overexpression of miR-223-3p in the CIH model could improve cognitive deficits and reduce the level of proinflammatory factors and pyroptosis factors in rats. Finally, based on silencing NLRP3 or overexpression miR-223-3p, we confirmed that there was a regulatory relationship between miR-223-3p and NLRP3. Our results suggested that the NLRP3/ miR-223-3p axis played a role in attenuating CIH-induced neuroinflammation.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

Functional & integrative genomics - 23(2023), 4 vom: 22. Nov., Seite 342

Sprache:

Englisch

Beteiligte Personen:

Wu, Cheng [VerfasserIn]
Xing, Wen [VerfasserIn]
Zhang, Yuanxiang [VerfasserIn]
Wang, Jue [VerfasserIn]
Zuo, Na [VerfasserIn]
Sun, Fuqin [VerfasserIn]
Liu, Qi [VerfasserIn]
Liu, Shaofeng [VerfasserIn]

Links:

Volltext

Themen:

CIH
EC 1.13.12.-
Journal Article
Luciferases
MIRN223 microRNA, rat
MiR-223-3p
MicroRNAs
NLR Family, Pyrin Domain-Containing 3 Protein
NLRP3
Neuroinflammation
Obstructive sleep apnea

Anmerkungen:

Date Completed 23.11.2023

Date Revised 12.12.2023

published: Electronic

Citation Status MEDLINE

doi:

10.1007/s10142-023-01268-w

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM364828099