TY - JOUR
T1 - Cholangiociliopathies
T2 - Genetics, molecular mechanisms and potential therapies
AU - Masyuk, Tatyana
AU - Masyuk, Anatoliy
AU - LaRusso, Nicholas
PY - 2009/5
Y1 - 2009/5
N2 - PURPOSE OF REVIEW: The present review summarizes recent knowledge on polycystic liver diseases (PCLDs), mechanisms of hepatic cystogenesis and potential therapies for these conditions. RECENT FINDINGS: PCLD may be classified as cholangiociliopathies. In PCLD associated with polycystic kidney disease, cell proliferation is one of the major mechanisms of cystogenesis, whereas in isolated PCLD (autosomal dominant polycystic liver disease), disrupted cell adhesion may be more important in cyst progression. In cystic cholangiocytes, overexpression of ion transporters and water channels facilitates fluid secretion into the cystic lumen, and growth factors, estrogens and cytokines promote cholangiocyte proliferation. With age, cholangiocytes lining liver cysts acquire features of mesenchymal cells contributing to hepatic fibrocystogenesis. A novel mechanism of liver cyst expansion in PCLD involves microRNA regulatory pathways. Hyperproliferation of cystic cholangiocytes is linked to abnormalities in cell cycle progression and microRNA expression. Decreased levels of miR-15a are coupled to upregulation of its target - the cell cycle regulator, Cdc25A. Cholangiocyte cilia in liver cysts are structurally abnormal. Somatostatin analogues and sirolimus reduce liver cyst volume in PCLD patients. SUMMARY: Clarification of molecular mechanisms of hepatic cystogenesis provides an opportunity for the development of targeted therapeutic options in PCLD.
AB - PURPOSE OF REVIEW: The present review summarizes recent knowledge on polycystic liver diseases (PCLDs), mechanisms of hepatic cystogenesis and potential therapies for these conditions. RECENT FINDINGS: PCLD may be classified as cholangiociliopathies. In PCLD associated with polycystic kidney disease, cell proliferation is one of the major mechanisms of cystogenesis, whereas in isolated PCLD (autosomal dominant polycystic liver disease), disrupted cell adhesion may be more important in cyst progression. In cystic cholangiocytes, overexpression of ion transporters and water channels facilitates fluid secretion into the cystic lumen, and growth factors, estrogens and cytokines promote cholangiocyte proliferation. With age, cholangiocytes lining liver cysts acquire features of mesenchymal cells contributing to hepatic fibrocystogenesis. A novel mechanism of liver cyst expansion in PCLD involves microRNA regulatory pathways. Hyperproliferation of cystic cholangiocytes is linked to abnormalities in cell cycle progression and microRNA expression. Decreased levels of miR-15a are coupled to upregulation of its target - the cell cycle regulator, Cdc25A. Cholangiocyte cilia in liver cysts are structurally abnormal. Somatostatin analogues and sirolimus reduce liver cyst volume in PCLD patients. SUMMARY: Clarification of molecular mechanisms of hepatic cystogenesis provides an opportunity for the development of targeted therapeutic options in PCLD.
KW - Cholangiociliopathies
KW - Fluid secretion
KW - Hepatic cystogenesis
KW - Proliferation
UR - http://www.scopus.com/inward/record.url?scp=67651101020&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67651101020&partnerID=8YFLogxK
U2 - 10.1097/MOG.0b013e328328f4ff
DO - 10.1097/MOG.0b013e328328f4ff
M3 - Review article
C2 - 19349863
AN - SCOPUS:67651101020
SN - 0267-1379
VL - 25
SP - 265
EP - 271
JO - Current Opinion in Gastroenterology
JF - Current Opinion in Gastroenterology
IS - 3
ER -