Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver.

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Gastroenterology. 2007

Jan;132(1):415-31.

Proliferating cholangiocytes:

a neuroendocrine compartment in the diseased liver.

Alvaro D, Mancino MG, Glaser S, Gaudio E, Marzioni M, Francis H, Alpini G.

Division of Gastroenterology & Clinical Medicine, Rome,

Italy.

In the last 15 years, the intrahepatic biliary tree has become the

object of extensive studies, which highlighted the extraordinary biologic

properties of cholangiocytes involved in bile

formation, proliferation, injury repair, fibrosis, angiogenesis, and regulation

of blood flow. Proliferation is a " typical "

property of cholangiocytes and is key as a mechanism

of repair responsible for maintaining the integrity of the biliary tree. Cholangiocyte proliferation

occurs virtually in all pathologic conditions of liver injury where it is

associated with inflammation, regeneration, and repair, thus conditioning the

evolution of liver damage. Interestingly, proliferating

cholangiocytes acquire the phenotype of neuroendocrine cells, and secrete different cytokines,

growth factors, neuropeptides, and hormones, which

represent potential mechanisms for cross talk with other liver cells. Many studies suggest the generation of a neuroendocrine compartment in the injured liver, mostly

constituted by cells with cholangiocyte features,

which functionally conditions the progression of liver disease. These insights on cholangiocyte pathophysiology will provide new potential strategies for

the management of chronic liver diseases. 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

biology.

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