MicroRNAs: Novel Targets in Hepatic Ischemia-Reperfusion Injury

Abstract

Hepatic ischemia-reperfusion injury (IRI) is one of the main factors for early allograft dysfunction (EAD), which may lead to graft rejection, graft loss, or shortened graft life in liver transplantation. Hepatic IRI appears to be inevitable during the majority of liver procurement and transportation of donor organs, resulting in a cascade of biological changes. The activation of signaling pathways during IRI results in the up- and downregulation of genes and microRNAs (miRNAs). miRNAs are ~21 nucleotides in length and well-characterized for their role in gene regulations; they have recently been used for therapeutic approaches in addition to their role as biomarkers for many diseases. miRNAs that are associated with hepatic IRI in in vitro and in vivo animal models are comprehensively summarized in this review. In those studies, the manipulation of miRNAs has been shown for the inhibition of aggravated immune response, reduction of apoptosis, stimulation of tissue repair, and enhancement of cell recovery to attenuate liver damage. Therefore, the utilization of liver-specific miRNA holds great potential as a therapeutic agent to improve early allograft dysfunction, hepatic injury, and patient outcome.

Keywords: biomarkers; inflammation; ischemia–reperfusion injury (IRI); liver transplantation; microRNA.

Figure 1

Differentially expressed miRNAs in hepatic IRI. miRNAs that are upregulated in hepatic IRI are indicated by green upward arrow, whereas miRNAs that are downregulated in hepatic IRI are indicated by downward red arrow. miRNAs that regulate NF-kB signaling are connected to NF-kB. For instance, miR-450-5b, miR-370, miR-34, miR-497-5p, and miR-128-3p are upregulated and inhibit their targets, causing an activation of NF-kB pathway during IRI. Reversely, miR-146a, miR-194, and miR-142-3p are downregulated in IRI, and their corresponding targets are upregulated, resulting in activation of NF-kB pathway.