Bile Acid-Mediated Interactions with Various Cell Types in the Cholestatic Liver.

Abstract

Bile acids (BAs) have garnered significant attention due to their novel roles in modulating diverse host physiological processes. They play a crucial role in nutrient transport, organelle function, and maintaining the systemic balance of pro/anti-inflammatory states. BAs exert complex physiological effects through their interaction with nuclear receptors, such as farnesoid X receptor or cell membrane receptor Takeda G protein-coupled receptor 5. Disruption of BA transport and homeostasis results in the accumulation of BAs and elevated concentrations in the systemic circulation. This contributes to the pathogenesis of cholestatic disorders and is implicated in a variety of liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis. In the context of cholestatic liver injury, BAs interact with parenchymal hepatocytes and nonparenchymal cells, leading to hepatocyte apoptosis, activation of hepatic stellate cells, and the initiation of inflammatory responses. Identifying key cellular and molecular components involved in this interaction may contribute to the development of potential therapies for cholestatic liver diseases. In this article, we provide a summary of the molecular mechanisms underlying BA-mediated interactions with various cell types in the cholestatic liver and discuss therapeutic strategies targeting BA pathways. We anticipate that a deeper understanding of these interactions will enable the formulation of novel strategies for the treatment of cholestatic liver injury.