Seminar

Role of primary cilium of cholangiocytes in the development of polycystic liver diseases and new therapeutic strategies

Jesús Bañales, PhD

The primary cilium of cholangiocytes (i.e. bile duct cells) is a tubular organelle extending from the apical membrane into the ductular lumen. Dr. Bañales recently reported that this organelle in normal conditions has mechano-, chemo-, and osmo-sensory features, detecting changes in bile, transmitting them into the cell and modifying cholangiocyte functions. Different genetic mutations trigger the cysts appearance and growth in Polycystic liver diseases (PCLDs), and in some cases this phenomenon is also associated with hepatic fibrosis. Mutations in genes that encode proteins localized in the cholangiocyte cilium result in physical and functional alterations of this organelle that induce the development of several forms of polycystic liver disease classified as "ciliopathies". PCLDs are characterized by bile-duct dilatation and/or cyst development, which become progressively more severe and requiring liver transplantation as the only therapeutic option. The large volume of hepatic cysts causes symptoms such as abdominal distension, local pressure with back pain, gastro-esophageal reflux, and dyspnea. It is estimated that 1 million people in the European Union are affected by PCLDs, and often, these patients also develop polycystic kidney disease. Dr. Bañales has recently demonstrated that hepatic cystogenesis in PCLDs is the result of hyper-proliferation, hypersecretion and alteration in the pattern of microRNAs in the bile duct cells (i.e. cholangiocytes), and that these alterations are intracellularly associated with an increase in the levels of 3',5'-adenosine monophosphate (cAMP) and a decrease in cytosolic free calcium. In this Seminar, Dr. Bañales will talk about the most interesting features of the primary cilium of cholangiocytes, the PCLDs pathology and the upcoming therapeutic strategies. Dr. Jesús M. Bañales obtained the Ph D in Biochemistry from the University of Navarra (2006). His research career has been focused on the study of the liver, and particularly the biliary epithelium. This work was carried out in national (CIMA and the University of Navarra) and international [Servier Laboratories (Paris), University of Colorado (Denver), and Mayo Clinic (Rochester MN)] centers of excellence. Currently, Dr. Bañales occupied an Ikerbasque research postion as the Head of the Liver Diseases Group at the Biodonostia Research Institute - Donostia University Hospital. His group is focused on the study of bile acids, lipids, metabolites and microRNAs on the regulation of liver function, as well as in pathological processes such as chronic liver damage, liver cancer, or aging.