Current Topics in TransplantationExperimental studiesMicroRNA-182-5p Ameliorates Liver Ischemia-Reperfusion Injury by Suppressing Toll-Like Receptor 4

- miR-182-5p reduces the inflammatory response in LPS-induced macrophages.
- miR-182-5p attenuates I/R injury in the murine liver by inactivating TLR4.
- miR-182-5p could attenuate hepatic I/R injury in a mouse model in vivo. The underlying mechanism of action appears to be inactivation of TLR4.

BackgroundToll-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.MethodsThe 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.ResultsTLR4 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.ConclusionsmiR-182-5p attenuates hepatic I/R by directly suppressing TLR4.