MicroRNA-182-5p Ameliorates Liver Ischemia-Reperfusion Injury by Suppressing Toll-Like Receptor 4.

Abstract

BACKGROUND:

Toll-like receptor 4 (TLR4) has received a lot of attention in studies on ischemia-reperfusion (I/R) injury. TLR4 is one of the target genes for microRNA-182-5p (miR-182-5p)-mediated regulation. In this study, we evaluated the role(s) of miR-182-5p transcriptional regulation in a hepatic I/R injury model in vivo and a lipopolysaccharide (LPS)-induced inflammatory reaction model in vitro.

METHODS:

The effects of miR-182-5p expression on the transcription and translation of TLR4 and several proinflammatory cytokines in a LPS-induced macrophage model were studied in vitro. After miR-182-5p was exogenously administered, the transcriptional/translational profile of TLR4 and the proinflammatory cytokines were evaluated in an in vivo I/R injury model. This data were combined with alanine transaminase expression levels and histologic features in an effort to understand the role(s) of miR-182-5p in a liver I/R model.

RESULTS:

TLR4 mRNA and protein levels in LPS-induced macrophages were significantly decreased in the presence of miR-182-5p (P < .01). In vivo TLR4 mRNA and protein levels as well as the induction of several proinflammatory cytokines, including tumor necrosis factor α and interleukin-6, were decreased in the presence of miR-182-5p. Hematoxylin and eosin staining showed that edema and necrosis in I/R modes were alleviated in the miR-182-5p-expressing group compared with control.

CONCLUSIONS:

miR-182-5p attenuates hepatic I/R by directly suppressing TLR4.

• Authors: W Jiang, G Liu, W Tang
• Journal: Transplantation proceedings (Transplant Proc) Vol. 48 Issue 8 Pg. 2809-2814 (Oct 2016) ISSN: 1873-2623 [Electronic] United States
• PMID: 27788822 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Interleukin-6
• Lipopolysaccharides
• MicroRNAs
• Mirn185 microRNA, mouse
• RNA, Messenger
• Tlr4 protein, mouse
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• interleukin-6, mouse

Topics

• Acute Lung Injury (pathology, prevention & control)
• Animals
• Cytokines (metabolism)
• Gene Expression Regulation
• Inflammation (pathology)
• Interleukin-6 (metabolism)
• Lipopolysaccharides (toxicity)
• Liver (pathology)
• Macrophages (metabolism)
• Male
• Mice, Inbred C57BL
• MicroRNAs (metabolism, pharmacology)
• RNA, Messenger (metabolism)
• Reperfusion Injury (pathology, prevention & control)
• Toll-Like Receptor 4 (antagonists & inhibitors)
• Tumor Necrosis Factor-alpha (metabolism)