Molecular insights on intracellular Wnt/β‐catenin signaling in alcoholic liver disease.

Alcoholic liver disease (ALD) is one of the most common health problems worldwide, especially in developing countries caused by chronic consumption of alcohol on a daily basis. The ALD spectrum is initiated with the early stages of alcoholic fatty liver (steatosis), progressing to alcoholic steatohepatitis, followed by the later stages of fibrosis and in some cases, cirrhosis and hepatocellular carcinoma (HCC). The Wnt/β‐catenin signaling required for healthy liver development, function, and regeneration is found to be aberrated in ALD, attributed to its progression. This review is to elucidate the association of Wnt/β‐catenin signaling with various stages of ALD progression. Alcohol causes downregulation of Wnt/β‐catenin signaling components and thereby suppressing the pathway. Reports have been published that aberrated Wnt/β‐catenin signaling, especially the absence of β‐catenin, results in decreased alcohol metabolism, causing steatosis followed by steatohepatitis via lipid accumulation, lipid peroxidation, liver injury, increased oxidative stress and apoptosis of hepatocytes, contributing to the advancement of ALD. Contrastingly, the progression of later stages of ALD like fibrosis and HCC depends on the increased activation of Wnt/β‐catenin signaling and its components. Existing studies reveal the varied expression of Wnt/β‐catenin signaling in ALD. However, the dual role of the Wnt/β‐catenin pathway in earlier and later stages of ALD is not clear. Therefore, studies on the Wnt/β‐catenin pathway and its components in various manifestations of ALD might provide insight in targeting the Wnt/β‐catenin pathway in ALD treatment. Significance Statement: This review discusses the importance of Wnt/β‐catenin signaling in the onset and progression of alcoholic liver disease (ALD) through various stages. Existing literature supports that the Wnt/β‐catenin signaling pathway plays a dual role during the earlier and advanced stages of ALD, which however remains unexplored in detail. This review also highlights the therapeutic opportunity associated with Wnt/β‐catenin signaling‐targeted ALD treatment. [ABSTRACT FROM AUTHOR]