title: Vasopressin regulates the growth of the biliary epithelium in polycystic liver disease.
abstract: The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium.
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, "Sapienza" University of Rome, Rome, Italy.
authors: Romina
authors: R
authors: Mancinelli
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, "Sapienza" University of Rome, Rome, Italy.|Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy.
authors: Antonio
authors: A
authors: Franchitto
authors: Department of Research, Central Texas Veterans Health Care System, Temple, TX, USA.|Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, TX, USA.|Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, Temple, TX, USA.
authors: Shannon
authors: S
authors: Glaser
authors: Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
authors: Antonella
authors: A
authors: Vetuschi
authors: Department of Research, Central Texas Veterans Health Care System, Temple, TX, USA.|Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, TX, USA.|Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, Temple, TX, USA.
authors: Julie
authors: J
authors: Venter
authors: Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, Temple, TX, USA.
authors: Roberta
authors: R
authors: Sferra
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, "Sapienza" University of Rome, Rome, Italy.
authors: Luigi
authors: L
authors: Pannarale
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, "Sapienza" University of Rome, Rome, Italy.
authors: Francesca
authors: F
authors: Olivero
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, "Sapienza" University of Rome, Rome, Italy.
authors: Guido
authors: G
authors: Carpino
authors: Department of Research, Central Texas Veterans Health Care System, Temple, TX, USA.|Baylor Scott & White Digestive Disease Research Center, Baylor Scott & White, Temple, TX, USA.|Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, Temple, TX, USA.
authors: Gianfranco
authors: G
authors: Alpini
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, "Sapienza" University of Rome, Rome, Italy.
authors: Paolo
authors: 0000-0002-7195-3760
authors: P
authors: Onori
authors: Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, "Sapienza" University of Rome, Rome, Italy.
authors: Eugenio
authors: E
authors: Gaudio
mesh_terms: D000818:Animals; D001653:Bile Ducts, Intrahepatic / Q000502:physiology*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D003560:Cysts / Q000378:metabolism / Q000503:physiopathology*; D004848:Epithelium / Q000254:growth & development*; D006801:Humans; D053539:Keratin-19 / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D011916:Rats, Inbred F344; D017483:Receptors, Vasopressin / Q000378:metabolism; D014667:Vasopressins / Q000502:physiology*
chemical_list: D053539:Keratin-19; D017483:Receptors, Vasopressin; D014667:Vasopressins; D000242:Cyclic AMP