MicroRNA-181b attenuates lipopolysaccharide-induced inflammatory responses in pulpitis via the PLAU/AKT/NF-κB axis

Copyright © 2023 Elsevier B.V. All rights reserved..

OBJECTIVE: This study aimed to investigate the role and underlying mechanisms of microRNA (miRNA)-181b in the inflammatory response in pulpitis.

METHODS: Quantitative reverse-transcription polymerase chain reaction (qRT-PCR), fluorescence in situ hybridization (FISH), and immunofluorescence techniques were used to determine the miRNA-181b and urokinase-type plasminogen activator (PLAU) expression levels in inflamed human dental pulp tissues (HDPTs) and lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs). The targets of miRNA-181b were identified and confirmed using a bioinformatics analysis, RNA sequencing, and dual-luciferase gene reporter assays. The effect of miRNA-181b or PLAU on proinflammatory cytokine expression in hDPCs was examined using qRT-PCR and western blotting. RNA sequencing was conducted to examine the signaling pathways implicated in miRNA-181b-mediated pulpitis. Western blotting and qRT-PCR were used to determine the miRNA-181b /PLAU/AKT/NF-κB signaling axis in pulpitis. A rat pulpitis model was created to observe the histopathological changes in the dental pulp tissue after the topical application of miRNA-181b agomir.

RESULTS: A significant decrease in miRNA-181b and an increase in PLAU were observed in HDPTs compared to the healthy controls, and these two factors showed a negative correlation. MiRNA-181b directly targeted PLAU. The miRNA-181b inhibitor resulted in a significant upregulation of IL-1β, IL-6 and TNF-α, whereas the knockdown of PLAU reversed this proinflammatory effect. Conversely, PLAU overexpression prevented the anti-inflammatory effects of the miRNA-181b mimics. Mechanistically, miRNA-181b inhibited the AKT/NF-κB pathway by targeting PLAU. In vivo application of the miRNA-181b agomir to inflamed pulp tissue alleviated inflammation.

CONCLUSION: MiRNA-181b targets PLAU, negatively regulating pro-inflammatory cytokine expression via the AKT/NF-κB signaling pathway.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:127

Enthalten in:

International immunopharmacology - 127(2024) vom: 25. Jan., Seite 111451

Sprache:

Englisch

Beteiligte Personen:

Meng, Tiantian [VerfasserIn]
Liu, Xinpai [VerfasserIn]
Zhang, Jing [VerfasserIn]
Li, Song [VerfasserIn]
He, Wei [VerfasserIn]
Li, Wuli [VerfasserIn]

Links:

Volltext

Themen:

AKT/NF-κB pathway
Cytokines
EC 2.7.11.1
EC 3.4.21.-
Inflammation
Journal Article
Lipopolysaccharides
MicroRNA-181b
MicroRNAs
NF-kappa B
PLAU
Plasminogen Activators
Proto-Oncogene Proteins c-akt
Pulpitis

Anmerkungen:

Date Completed 18.01.2024

Date Revised 18.01.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.intimp.2023.111451

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM366448544