1. Role of Bile Acids and Bile Salts in Acute Pancreatitis: From the Experimental to Clinical Studies
- Author
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Julia Doller, Franziska Gisela Thiel, Frank Ulrich Weiss, Ali A. Aghdassi, M. Wiese, Anika Wilden, Laura L. De Freitas Chama, Markus M. Lerch, Robert Bolsmann, Matthias Sendler, Van Huy Tran, Jana Marielle Modenbach, Juliane Glaubitz, and Quang Trung Tran
- Subjects
acinar cells ,BAs - bile acids ,Endocrinology, Diabetes and Metabolism ,UDCA - ursodeoxycholic acid ,Pharmacology ,Endoplasmic Reticulum ,TUDCA - tauroursodeoxycholic acid ,PI3K - phosphatidylinositol 3-kinase ,RyR - ryanodine receptor ,0302 clinical medicine ,Endocrinology ,CDCA - chenodeoxycholic acid ,NaT - sodium taurocholate ,Receptor ,Ca2 + ,IP3R - inositol triphosphate receptors ,Ryanodine receptor ,Chemistry ,SERCA - sarco/endoplasmic reticulum Ca2+ ,gallstone ,[Ca2+]i - intracellular calcium concentration ,Mitochondria ,Gpbar1 - G-protein–coupled bile acid receptor 1 ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,TCA - taurocholic acid ,Pancreas ,Signal Transduction ,Cell signaling ,acute pancreatitis ,FXR - farnesoid X receptor ,education ,TLCS - taurolithocholic acid-3-sulfate ,Reviews ,Bile Acids and Salts ,03 medical and health sciences ,Necrosis ,Internal Medicine ,medicine ,Acinar cell ,AP - acute pancreatitis ,Animals ,Humans ,TCDC - taurochenodeoxycholic acid ,ATP - adenosine triphosphate ,bile acids ,Hepatology ,Endoplasmic reticulum ,Membrane Transport Proteins ,Inositol trisphosphate receptor ,NTCP - NaT cotransporting polypeptide ,Cytosol ,Disease Models, Animal ,Pancreatitis ,Calcium ,IL - interleukin ,CCK - cholecystokinin - Abstract
Acute pancreatitis (AP) is one of the most common gastroenterological disorders leading to hospitalization. It has long been debated whether biliary AP, about 30% to 50% of all cases, is induced by bile acids (BAs) when they reach the pancreas via reflux or via the systemic blood circulation. Besides their classical function in digestion, BAs have become an attractive research target because of their recently discovered property as signaling molecules. The underlying mechanisms of BAs have been investigated in various studies. Bile acids are internalized into acinar cells through specific G-protein–coupled BA receptor 1 and various transporters. They can further act via different receptors: the farnesoid X, ryanodine, and inositol triphosphate receptor. Bile acids induce a sustained Ca2+ influx from the endoplasmic reticulum and release of Ca2+ from acidic stores into the cytosol of acinar cells. The overload of intracellular Ca2+ results in mitochondrial depolarization and subsequent acinar cell necrosis. In addition, BAs have a biphasic effect on pancreatic ductal cells. A more detailed characterization of the mechanisms through which BAs contribute to the disease pathogenesis and severity will greatly improve our understanding of the underlying pathophysiology and may allow for the development of therapeutic and preventive strategies for gallstone-inducedAP.
- Published
- 2020