PMID- 38154211
OWN - NLM
STAT- MEDLINE
DCOM- 20240118
LR  - 20240118
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 127
DP  - 2024 Jan 25
TI  - MicroRNA-181b attenuates lipopolysaccharide-induced inflammatory responses in 
      pulpitis via the PLAU/AKT/NF-kappaB axis.
PG  - 111451
LID - S1567-5769(23)01778-2 [pii]
LID - 10.1016/j.intimp.2023.111451 [doi]
AB  - 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-kappaB 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-1beta, IL-6 and TNF-alpha, 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-kappaB 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-kappaB signaling pathway.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Meng, Tiantian
AU  - Meng T
AD  - College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral 
      Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, 
      China. Electronic address: 599754092@qq.com.
FAU - Liu, Xinpai
AU  - Liu X
AD  - College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral 
      Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, 
      China. Electronic address: 296460752@qq.com.
FAU - Zhang, Jing
AU  - Zhang J
AD  - College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral 
      Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, 
      China. Electronic address: 253234653@qq.com.
FAU - Li, Song
AU  - Li S
AD  - College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral 
      Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, 
      China. Electronic address: 3197053337@qq.com.
FAU - He, Wei
AU  - He W
AD  - College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral 
      Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, 
      China; School of Basic Medical Sciences, Anhui Medical University, 81#Mei Shan 
      Road, Hefei 230032, Anhui, China. Electronic address: weihe@ahmu.edu.cn.
FAU - Li, Wuli
AU  - Li W
AD  - College & Hospital of Stomatology, Anhui Medical University, Key Lab. of Oral 
      Diseases Research of Anhui Province, 69# Mei Shan Road, Hefei 230032, Anhui, 
      China. Electronic address: hotspot2008@163.com.
LA  - eng
PT  - Journal Article
DEP - 20231227
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (NF-kappa B)
RN  - 0 (Lipopolysaccharides)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.21.- (Plasminogen Activators)
RN  - 0 (MicroRNAs)
RN  - 0 (Cytokines)
SB  - IM
MH  - Rats
MH  - Humans
MH  - Animals
MH  - NF-kappa B/metabolism
MH  - *Pulpitis
MH  - Lipopolysaccharides
MH  - Proto-Oncogene Proteins c-akt/genetics
MH  - Plasminogen Activators/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - *MicroRNAs/genetics/metabolism
MH  - Cytokines/genetics
OTO - NOTNLM
OT  - AKT/NF-kappaB pathway
OT  - Inflammation
OT  - PLAU
OT  - Pulpitis
OT  - microRNA-181b
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/12/29 00:42
MHDA- 2024/01/18 06:42
CRDT- 2023/12/28 18:02
PHST- 2023/08/12 00:00 [received]
PHST- 2023/12/17 00:00 [revised]
PHST- 2023/12/23 00:00 [accepted]
PHST- 2024/01/18 06:42 [medline]
PHST- 2023/12/29 00:42 [pubmed]
PHST- 2023/12/28 18:02 [entrez]
AID - S1567-5769(23)01778-2 [pii]
AID - 10.1016/j.intimp.2023.111451 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2024 Jan 25;127:111451. doi: 10.1016/j.intimp.2023.111451. 
      Epub 2023 Dec 27.