Polycystic Liver Disease

Polycystic liver diseases, a group of genetic cholangiopathies, are characterized by progressive dilatation of biliary epithelial cysts. The dominant pathology of the adult polycystic kidney (ADPKD) is caused by mutations in the genes that code for ciliary proteins, polycystins. Polycystins function as mechanoreceptors but are also involved in cell differentiation and epithelial morphogenesis. Our recent studies show that angiogenic growth factors, in particular VEGF and Angiopoietin-1, are overexpressed in ADPKD epithelial bile cells (cholangiocytes) and may play a role in the pathogenesis of liver disease. Starting from these observations, the hypothesis of this project is that the autocrine and paracrine angiogenetic signals produced by the biliary epithelium are the key responsible for the growth of liver cysts and the progression of the disease in ADPKD.

These studies will allow us to understand the basic mechanisms responsible for the pathogenesis of polycystic liver disease and to device pharmacological strategies useful as disease therapy. The results will also have a more general relevance to better understand the fundamental mechanisms that regulate angiogenesis in liver diseases.