MicroRNA-141-3p Attenuates Oxidative Stress-induced Hepatic Ischemia Reperfusion Injury via Keap1/Nrf2 Pathway

Abstract

Hepatic ischemia reperfusion injury (IRI) is a major factor affecting the prognosis of liver transplantation through a series of severe cell death and inflammatory responses. MicroRNA-141-3p (miR-141-3p) has been reported to be associated with hepatic steatosis and other liver diseases. However, the potential role of miR-141-3p in hepatic IRI is currently unknown. In the present study, we found that miR-141-3p levels were negatively correlated with alanine aminotransferase (ALT)/aspartate aminotransferase (AST) in liver transplantation patients. The results demonstrated that miR-141-3p was decreased in mouse liver tissue after hepatic IRI in mice and in hepatocytes after hypoxia/reoxygenation (H/R). Overexpression of miR-141-3p directly decreased Kelch-like ECH-associated protein 1 (Keap1) levels and attenuated cell apoptosis in vivo and in vitro, while inhibition of miR-141-3p facilitated apoptosis. Further experiments revealed that overexpression of miR-141-3p also attenuated oxidative stress-induced damage in hepatocytes under H/R conditions. Taken together, our results indicate that miR-141-3p plays a major role in hepatic IRI through the Keap1 signaling pathway, and the present study suggests that miR-141-3p might have a protective effect on hepatic IRI to some extent.

Non-coding RNAs: The potential biomarker or therapeutic target in hepatic ischemia-reperfusion injury

“…Only two miRNAs (miR-141-3p and miR-192-5p) have been identified in humans. Li et al [ 88 ] collected serum samples from 27 Liver transplantation patients at different time points (pre-operatively, 4 h after reperfusion, and on postoperative days 1, 2, and 3) and measured the expression of miR-141-3p, ALT, and AST. They found that 4 h after perfusion, miR-141-3p was lower than pre-operation and then gradually increased over time, which manifested a negative correlation with ALT/AST levels[ 87 ].…”

“…Roy and his colleagues detected miR-192-5p expression in the liver tissues and sera of patients with acute liver injury. The results shown that miR-192-5p decreased in liver samples, but elevated in serum levels from patients with acute hepatic injury; further investigation revealed that miR-192-5p concentrations in serum were positively correlated with AST, ALT, and miR-122 Levels, which might represent a hepatocyte-specific serum biomarker[ 88 ].…”