Extracellular RNAs/TLR3 signaling contributes to acute intestinal injury induced by intestinal ischemia reperfusion in mice

Copyright © 2023. Published by Elsevier B.V..

Toll-like receptor 3 (TLR3), one pattern recognition receptor activated by viral and endogenous RNA, has been recently reported to regulate ischemia/reperfusion (I/R) injury in various organs. However, the role of TLR3 in the development of intestinal I/R injury remains unclear. The aim of this study is to evaluate the effects of extracellular RNAs/TLR3 signaling in intestinal I/R injury. An intestinal I/R injury model was established with superior mesenteric artery occlusion both in wild-type and TLR3 knockout (KO, -/-) mice, and MODE-K cells were subjected to hypoxia/reoxygenation (H/R) to mimic the I/R model in vivo. Extracellular RNAs (exRNAs), especially double-stranded RNAs (dsRNAs) co-localized with TLR3, were significantly increased both in vitro and in vivo. Compared with wild-type mice, TLR3 knockout obviously attenuated intestinal I/R injury. Both TLR3/dsRNA complex inhibitor and TLR3 siRNA administration reduced TLR3 expressions and subsequently inhibited intestinal inflammatory cytokine production and apoptosis. In conclusion, exRNAs/TLR3 signaling is a key mechanism that regulates intestinal I/R injury in adult mice, and the TLR3/dsRNA complex inhibitor can be an effective approach for attenuating intestinal I/R-induced inflammatory response and apoptosis.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:1869

Enthalten in:

Biochimica et biophysica acta. Molecular basis of disease - 1869(2023), 7 vom: 01. Okt., Seite 166790

Sprache:

Englisch

Beteiligte Personen:

Lei, Yu-Qiong [VerfasserIn]
Wan, Yan-Tong [VerfasserIn]
Liang, Guang-Tao [VerfasserIn]
Huang, Yu-Hao [VerfasserIn]
Dong, Peng [VerfasserIn]
Luo, Si-Dan [VerfasserIn]
Zhang, Wen-Juan [VerfasserIn]
Liu, Wei-Feng [VerfasserIn]
Liu, Ke-Xuan [VerfasserIn]
Zhang, Xi-Yang [VerfasserIn]

Links:

Volltext

Themen:

63231-63-0
Apoptosis
Double-stranded RNAs
Extracellular RNAs
Inflammation
Intestine
Ischemia/reperfusion
Journal Article
RNA
Research Support, Non-U.S. Gov't
TLR3 protein, mouse
Toll-Like Receptor 3
Toll-like receptor 3

Anmerkungen:

Date Completed 07.08.2023

Date Revised 07.08.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.bbadis.2023.166790

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM358379059