@article{TCR17797,
author = {Huayu Yang and Chang Li and Wei Huang and Wei Guo and Jingrong Cui and Xinting Sang and Yilei Mao},
title = {Wip1−/− ameliorates hepatic ischemia/reperfusion injury via PI3K/ Akt activation},
journal = {Translational Cancer Research},
volume = {6},
number = {6},
year = {2017},
keywords = {},
abstract = {Background: Liver is the largest organ in the body. It constitutes 2.5% of the body weight and receives approximately 25% of the cardiac output via both the dual blood flow and the portal vein as well as the hepatic artery, the latter of which contributes to 75–80% of the total flow and >50% of the total oxygen supply. Warm ischemia/reperfusion (I/R) injury is a common acute liver injury in clinical scenario. The Pringle manoeuvre in many liver surgeries is one of the many causes. By now researchers have found out that I/R can be mediated by many mechanisms including the pressure change in liver sinusoids mediated by sinusoidal endothelial cells (SEC) and nitric oxide (NO), innate immunity regulation by Kupffer cell, ATP-depletion-dependent liver cell necrosis and caspase-dependent apoptosis. Akt is a serine/threonine kinase which plays a critical role in regulating various biological processes including apoptosis, autophagy, cell growth, regeneration and protein synthesis. It has been revealed that Akt activates downstream proteins like Bad to regulate pathogenesis of liver I/R injury. Wip1 (wild-type p53 induced phosphatase 1), another serine/threonine phosphatase, plays a key role in immunity and inflammation. However, it still remains mystery whether wip1 is involved in pathogenesis and progression of liver I/R injury. In this study, we were aimed to discover the functional role of wip1 gene in acute liver injury and the possible underlying mechanisms.
Methods: We used partial (2/3) liver warm I/R injury model and established wip1 knock-out mice to investigate the expression of wip1 and its impact on pathological changes after I/R injury. Moreover, we used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and western blot to study if PI3K/Akt and apoptotic pathway was affected by wip1 expression following liver injury.
Results: We have found that wip1 expression level was significantly reduced after I/R injury in wild-type mice, whereas in wip1 knock-out mice, the serum levels of alanine aminotransferase (ALT) were significantly decreased (851.3±270.9 U/L) compared with wild-type mice (1172.5±237.1 U/L) (P},
issn = {2219-6803}, url = {https://tcr.amegroups.org/article/view/17797}
}