Zinc Finger E‐Box Binding Homeobox 1 Mediates Alcohol‐Induced Liver Disease

ABSTRACT Hepatitis resulting from alcoholic liver disease (ALD) is an important risk factor for liver cancer. It is essential to understand the role of ALD to prevent liver cancer. Zinc finger E‐box binding homeobox 1 (ZEB1) is a well‐known transcription factor that can trigger tumorigenesis. However, how ZEB1 affects liver hepatitis related to ALD remains unclear. We used western blot, immunohistochemistry, and quantitative real‐time polymerase chain reaction to detect ZEB1, IL‐1β, MCP‐1, and YAP expression in the liver tissue of a mouse ALD model and in L02 cells treated with alcohol. We used flow cytometric analysis to detect the apoptosis ratio of L02 cells. Levels of IL‐1β and MCP‐1 increased in the liver tissue of the mouse ALD model, which indicated that ALD triggered hepatic inflammation. ZEB1 was upregulated in the liver tissue of the mouse ALD model and in the L02 cells treated with alcohol. We also examined how ZEB1 regulates liver hepatitis. The results showed that levels of IL‐1β and MCP‐1 were increased by ZEB1. Knockdown of ZEB1 decreased the ratio of apoptotic cells. Moreover, the pattern of YAP expression was completely consistent with the ZEB1 expression pattern, and we verified that ZEB1 unregulated the YAP1 level. Finally, we used verteporfin (VP), an inhibitor of YAP, to treat ZEB1‐overpressing L02 cells. We found that VP suppressed the level of inflammation in alcohol‐treated L02 cells induced by ZEB1 overexpression. ZEB1‐YAP‐IL‐1β/MCP‐1 may be a critical pathway in ALD development. ZEB1 is a crucial mediator of alcoholic liver disease.