Bile Acid Metabolism and Signaling in Cholestasis, Inflammation, and Cancer.

摘要: Bile acids are synthesized from cholesterol in the liver. Some cytochrome P450 (CYP) enzymes play key roles bile acid synthesis. physiological detergent molecules, so highly cytotoxic. They undergo enterohepatic circulation and important generating flow facilitating biliary secretion of endogenous metabolites xenobiotics intestinal absorption dietary fats lipid-soluble vitamins. synthesis, transport, pool size therefore tightly regulated under conditions. In cholestasis, impaired leads to accumulation liver, causing hepatocyte injury inflammation. Chronic cholestasis is associated with fibrosis, cirrhosis, eventually liver failure. also increases risk developing hepatocellular or cholangiocellular carcinomas. Extensive research last two decades has shown that act as signaling molecules regulate various cellular processes. The acid-activated nuclear receptors ligand-activated transcriptional factors critical regulation acid, drug, xenobiotic metabolism. these a network genes involved conjugation, metabolism alleviate acid-induced inflammation injury. Additionally, known cell growth proliferation, altered levels diseased conditions have been implicated injury/regeneration tumorigenesis. We will cover mechanisms homeostasis detoxification during initiation hepatic inflammation, regeneration, carcinogenesis.