Polycystic Liver Diseases: Congenital Disorders of Cholangiocyte Signaling

Article ID	Journal	Published Year	Pages	File Type
3292994	Gastroenterology	2011	6 Pages	PDF

Abstract

Polycystic liver diseases (PLD) are inherited disorders of the biliary epithelium, caused by genetic defects in proteins associated with intracellular organelles, mainly the endoplasmic reticulum and the cilium. PLD are characterized by the formation and progressive enlargement of multiple cysts scattered throughout the liver parenchyma, and include different entities, classified based on their pathology, inheritance pattern, involvement of the kidney and clinical features. PLD should be considered as congenital diseases of cholangiocyte signaling. Here, we will review the changes in signaling pathways involved in liver cyst formation and progression, and their impact on cholangiocyte physiology. Each pathway represents a potential target for therapies aimed at reducing disease progression.

Keywords

ARPKD IGF-1 CFTR RyR ChF ECM IP3R HIF dpm adenyl cyclase ADPKD PCLD SEC63 PRKCSH PC2 PC1 AC6 HNF-1β pKa RAF mTOR EGF MMP PLD cAMP ERK1/2 v-akt murine thymoma viral oncogene homolog 1 Akt interleukin Caroli disease polycystic liver disease autosomal-dominant polycystic kidney disease autosomal-recessive polycystic kidney disease cystic fibrosis transmembrane conductance regulator endoplasmic reticulum epidermal growth factor Hypoxia-inducible factor Vascular endothelial growth factor Vascular Endothelial Growth Factor (VEGF)insulin-like growth factor 1 congenital hepatic fibrosis Extracellular matrix matrix metalloproteinase MEK Ductal plate malformation mammalian target of rapamycin Transient receptor potential vanilloid 4 protein kinase A mitogen-activated protein kinase kinase Polycystin-1 Polycystin-2 Inositol 1,4,5-trisphosphate receptor Ryanodine receptor