Expression of aVB6 integrin by Pkhd1-defective cholangiocytes links enhanced ductal secretion of Macrophage chemokines to progressive portal fibrosis in Congenital Hepatic Fibrosis

8 Introduction 10 1. The liver 11 1.1 Liver organization and function 11 1.2 The cholangiocytes and the biliary system 13 2. Pathogenetic mechanisms of cholangiopathies 16 3. Hepatic fibrosis 18 3.1 Pathogenesis of liver fibrosis 18 3.2 Cellular elements involved in liver fibrosis 22 3.3 Liver fibrosis and αvβ6 integrin 27 3.4 Experimental models of liver fibrosis 30 4. Genetic cholangiopathies: Autosomal Recessive Polycystic Kidney Disease (ARPKD), Congenital Hepatic Fibrosis (CHF) and Caroli Disease (CD) 32 4.1 Fibrocystin 34 AIMS 36 METHODS 38 Experimental mouse model of liver fibrosis 39 Sirius red to evaluate fibrosis extension 39 Spleen weight quantification 40