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Wnt-beta-catenin Signaling Protects Against Hepatic Ischemia and Reperfusion Injury in Mice GASTROENTEROLOGY Lehwald, N., Tao, G., Jang, K. Y., Sorkin, M., Knoefel, W. T., Sylvester, K. G. 2011; 141 (2): 707-U417


Ischemia and reperfusion injury are common causes of oxidative tissue damage associated with many liver diseases and hepatic surgery. The Wnt-ß-catenin signaling pathway is an important regulator of hepatic development, regeneration, and carcinogenesis. However, the role of Wnt signaling in the hepatocellular response to ischemia-reperfusion (I/R) injury has not been determined.Hepatic injury following ischemia or I/R was investigated in hepatocyte-specific, ß-catenin-deficient mice, as well as Wnt1-overexpressing and wild-type (control) mice.Wnt-ß-catenin signaling was affected by the cellular redox balance in hepatocytes. Following ischemia or I/R, mice with ß-catenin-deficient hepatocytes were significantly more susceptible to liver injury. Conversely, mice that overexpressed Wnt1 in hepatocytes were resistant to hepatic I/R injury. Hypoxia inducible factor (HIF)-1a signaling was reduced in ß-catenin-deficient liver but increased in hepatocytes that overexpressed Wnt1 under hypoxia and following I/R, indicating an interaction between ß-catenin and HIF-1a signaling in the liver. The mechanism by which Wnt signaling protects against liver injury involves the role of ß-catenin as a transcriptional coactivator of HIF-1a signaling, which promotes hepatocyte survival under hypoxic conditions.Cellular redox balance affects Wnt-ß-catenin signaling, which protects against hypoxia and I/R injury. These findings might be used to develop strategies for protection of hepatocytes, regeneration of liver, and inhibition of carcinogenesis.

View details for DOI 10.1053/j.gastro.2011.04.051

View details for Web of Science ID 000293523300049

View details for PubMedID 21679710

View details for PubMedCentralID PMC4084974