Polycystic liver diseases

Onori, P.; Franchitto, A.; Mancinelli, R.; Carpino, G.; Alvaro, D.; Francis, H.; Alpini, G.; Gaudio, E.

doi:10.1016/j.dld.2010.01.006

« Previous Next »Digestive and Liver Disease
Volume 42, Issue 4 , Pages 261-271, April 2010

Polycystic liver diseases

P. Onori
- Experimental Medicine, University of L’Aquila, L’Aquila, Italy
A. Franchitto
- Dept Human Anatomy, University of Rome “La Sapienza”, Rome, Italy
R. Mancinelli
- Dept Human Anatomy, University of Rome “La Sapienza”, Rome, Italy
G. Carpino
- Dept Health Science, University of Rome “Foro Italico”, Italy
D. Alvaro
- Gastroenterology, Polo Pontino, University of Rome “La Sapienza”, Rome, Italy
H. Francis
- Research, Central Texas Veterans Health Care System, USA
G. Alpini
- Research, Central Texas Veterans Health Care System, USA
- Scott & White Digestive Disease Research Center, Texas A&M Health Science Center, College of Medicine, USA
E. Gaudio
- Dept Human Anatomy, University of Rome “La Sapienza”, Rome, Italy
- Corresponding author. Tel.: +39 0649918060; fax: +39 0649918062.

Received 23 November 2009; accepted 7 January 2010. published online 08 February 2010.

Abstract

Polycystic liver diseases (PCLDs) are genetic disorders with heterogeneous etiologies and a range of phenotypic presentations. PCLD exhibits both autosomal or recessive dominant pattern of inheritance and is characterized by the progressive development of multiple cysts, isolated or associated with polycystic kidney disease, that appear more extensive in women. Cholangiocytes have primary cilia, functionally important organelles (act as mechanosensors) that are involved in both normal developmental and pathological processes. The absence of polycystin-1, 2, and fibrocystin/polyductin, normally localized to primary cilia, represent a potential mechanism leading to cyst formation, associated with increased cell proliferation and apoptosis, enhanced fluid secretion, abnormal cell–matrix interactions, and alterations in cell polarity. Proliferative and secretive activities of cystic epithelium can be regulated by estrogens either directly or by synergizing growth factors including nerve growth factor, IGF1, FSH and VEGF.

The abnormalities of primary cilia and the sensitivity to proliferative effects of estrogens and different growth factors in PCLD cystic epithelium provide the morpho-functional basis for future treatment targets, based on the possible modulation of the formation and progression of hepatic cysts.

Keywords: Cystic epithelium, Estrogen, FSH, IGF-1, Polycystic liver, Polycystin, Primary cilium, VEGF