title: Recent advances on the mechanisms regulating cholangiocyte proliferation and the significance of the neuroendocrine regulation of cholangiocyte pathophysiology.
abstract: Cholangiocytes are epithelial cells lining the biliary epithelium. Cholangiocytes play several key roles in the modification of ductal bile and are also the target cells in chronic cholestatic liver diseases (i.e., cholangiopathies) such as PSC, PBC, polycystic liver disease (PCLD) and cholangiocarcinoma (CCA). During these pathologies, cholangiocytes (which in normal condition are in a quiescent state) begin to proliferate acquiring phenotypes of neuroendocrine cells, and start secreting different cytokines, growth factors, neuropeptides, and hormones to modulate cholangiocytes proliferation and interaction with the surrounding environment, trying to reestablish the balance between proliferation/loss of cholangiocytes for the maintenance of biliary homeostasis. The purpose of this review is to summarize the recent findings on the mechanisms regulating cholangiocyte proliferation and the significance of the neuroendocrine regulation of cholangiocyte pathophysiology. To clarify the mechanisms of action of these factors we will provide new potential strategies for the management of chronic liver diseases.
authors.affiliation: 1 Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome "Sapienza", Rome, Italy ; 2 Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy ; 3 Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy ; 4 Department of Health Science, University of Rome "Foro Italico", Italy ; 5 Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza, University of Rome "Sapienza", Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Franchitto
authors.affiliation: 1 Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome "Sapienza", Rome, Italy ; 2 Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy ; 3 Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy ; 4 Department of Health Science, University of Rome "Foro Italico", Italy ; 5 Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza, University of Rome "Sapienza", Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Onori
authors.affiliation: 1 Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome "Sapienza", Rome, Italy ; 2 Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy ; 3 Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy ; 4 Department of Health Science, University of Rome "Foro Italico", Italy ; 5 Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza, University of Rome "Sapienza", Rome, Italy.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Renzi
authors.affiliation: 1 Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome "Sapienza", Rome, Italy ; 2 Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy ; 3 Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy ; 4 Department of Health Science, University of Rome "Foro Italico", Italy ; 5 Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza, University of Rome "Sapienza", Rome, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Carpino
authors.affiliation: 1 Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome "Sapienza", Rome, Italy ; 2 Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy ; 3 Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy ; 4 Department of Health Science, University of Rome "Foro Italico", Italy ; 5 Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza, University of Rome "Sapienza", Rome, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Mancinelli
authors.affiliation: 1 Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome "Sapienza", Rome, Italy ; 2 Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy ; 3 Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy ; 4 Department of Health Science, University of Rome "Foro Italico", Italy ; 5 Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza, University of Rome "Sapienza", Rome, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Alvaro
authors.affiliation: 1 Department of Anatomical, Histological, Forensic Medicine and Orthopedic Sciences, University of Rome "Sapienza", Rome, Italy ; 2 Eleonora Lorillard Spencer-Cenci Foundation, Rome, Italy ; 3 Department of Experimental Medicine, University of L'Aquila, L'Aquila, Italy ; 4 Department of Health Science, University of Rome "Foro Italico", Italy ; 5 Department of Medico-Surgical Sciences and Biotechnologies, Polo Pontino, Sapienza, University of Rome "Sapienza", Rome, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Gaudio
keywords: Biliary tree; cholangiocytes; liver; neuroendocrine regulation; proliferation