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Role of follicle‐stimulating hormone on biliary cyst growth in autosomal dominant polycystic kidney disease
Author(s) -
Onori Paolo,
Mancinelli Romina,
Franchitto Antonio,
Carpino Guido,
Renzi Anastasia,
Brozzetti Stefania,
Venter Julie,
Francis Heather,
Glaser Shan,
Jefferson Douglas M.,
Alpini Gianfranco,
Gaudio Eugenio
Publication year - 2013
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12177
Subject(s) - polycystic liver disease , cholangiocyte , endocrinology , medicine , autosomal dominant polycystic kidney disease , follicle stimulating hormone , mapk/erk pathway , biology , polycystic kidney disease , cyst , follicle stimulating hormone receptor , kidney , cancer research , hormone , luteinizing hormone , kinase , pathology , microbiology and biotechnology , transplantation , liver transplantation
Background Autosomal dominant polycystic kidney disease ( ADPKD ) is a common genetic disorder characterized by the progressive development of renal and hepatic cysts. Follicle‐stimulating hormone ( FSH ) has been demonstrated to be a trophic factor for biliary cells in normal rats and experimental cholestasis induced by bile duct ligation ( BDL ). Aims To assess the effect of FSH on cholangiocyte proliferation during ADPKD using both in vivo and in vitro models. Methods Evaluation of FSH receptor ( FSHR ), FSH, phospho‐extracellular‐regulated kinase ( pERK ) and c‐myc expression in liver fragments from normal patients and patients with ADPKD . In vitro , we studied proliferating cell nuclear antigen ( PCNA ) and cAMP levels in a human immortalized, non‐malignant cholangiocyte cell line (H69) and in an immortalized cell line obtained from the epithelium lining the hepatic cysts from the patients with ADPKD ( LCDE ) with or without transient silencing of the FSH gene. Results Follicle‐stimulating hormone is linked to the active proliferation of the cystic wall and to the localization of p‐ERK and c‐myc. This hormone sustains the biliary growth by activation of the cAMP/ERK signalling pathway. Conclusion These results showed that FSH has an important function in cystic growth acting on the cAMP pathway, demonstrating that it provides a target for medical therapy of hepatic cysts during ADPKD .