Functional and structural features of cholangiocytes in health and disease.
Cholangiocytes are the epithelial cells that line the bile ducts. Along the biliary tree, two different kinds of cholangiocytes exist; small and large cholangiocytes. Each type has important differences in their biological role in physiological and pathological conditions. In response to injury, cholangiocytes become reactive and acquire a neuroendocrine-like phenotype with the secretion of a number of peptides. These molecules act in an autocrine/paracrine fashion to modulate cholangiocyte biology and determine the evolution of biliary damage. The failure of such mechanisms is believed to influence the progression of cholangiopathies, a group of diseases that selectively target biliary cells. Therefore, the understanding of mechanisms regulating cholangiocyte response to injury is expected to foster the development of new therapeutic options to treat biliary diseases. In the present review, we will discuss the most recent findings in the mechanisms driving cholangiocyte adaptation to damage, with particular emphasis on molecular pathways that are susceptible of therapeutic intervention. Morphogenic pathways (Hippo, Notch, Hedgehog), which have been recently shown to regulate biliary ontogenesis and response to injury, will also be reviewed. In addition, the results of ongoing clinical trials evaluating new drugs for the treatment of cholangiopathies will be discussed.
Department of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy.
Luca
L
Maroni
Scott & White Digestive Disease Research Center, Scott & White, Texas A&M University Health Science Center, Temple, TX 76504.
Bai
B
Haibo
Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, Temple, TX 76504.
Debolina
D
Ray
Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, Temple, TX 76504.
Tianhao
T
Zhou
Scott & White Digestive Disease Research Center, Scott & White, Texas A&M University Health Science Center, Temple, TX 76504.
Ying
Y
Wan
Research, Central Texas Veterans Health Care System, Texas A&M University Health Science Center, Temple, TX 76504 ; Scott & White Digestive Disease Research Center, Scott & White, Texas A&M University Health Science Center, Temple, TX 76504 ; Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, Temple, TX 76504.
Fanyin
F
Meng
Department of Gastroenterology and Hepatology, Università Politecnica delle Marche, Ancona, Italy.
Marco
M
Marzioni
Research, Central Texas Veterans Health Care System, Texas A&M University Health Science Center, Temple, TX 76504 ; Scott & White Digestive Disease Research Center, Scott & White, Texas A&M University Health Science Center, Temple, TX 76504 ; Department of Medicine, Division Gastroenterology, Texas A&M University Health Science Center, Temple, TX 76504.
Gianfranco
G
Alpini
Biliary Epithelium; Primary Biliary Cirrhosis; Primary Sclerosing Cholangitis