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Cholangiocyte proliferation and liver fibrosis

Published online by Cambridge University Press:  25 February 2009

Shannon S. Glaser ,
Eugenio Gaudio ,
Tim Miller ,
Domenico Alvaro  and
Gianfranco Alpini
Shannon S. Glaser*
Affiliation:
Department of Medicine, Scott and White and Texas A&M Health Science Center, Temple, TX 76504, USA.
Eugenio Gaudio
Affiliation:
Department of Anatomy, Sapienza University of Rome, Via Alfonso Borelli 50, 00161 Rome, Italy.
Tim Miller
Affiliation:
Department of Medicine, Scott and White and Texas A&M Health Science Center, Temple, TX 76504, USA.
Domenico Alvaro
Affiliation:
Division of Gastroenterology, Sapienza University of Rome, Polo Pontino, Via R. Rossellini 51, 00137 Rome, Italy.
Gianfranco Alpini
Affiliation:
Department of Medicine, Scott and White and Texas A&M Health Science Center, Temple, TX 76504, USA.
*
*Corresponding author: Medical Research Building Room 316B, Scott and White and Texas A&M Health Science Center, 702 SW HK Dodgen Loop, Temple, TX 76504, USA. Tel: +1 254 742 7058; Fax: +1 254 724 5944; E-mail: sglaser@tamu.edu
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Abstract

Cholangiocyte proliferation is triggered during extrahepatic bile duct obstruction induced by bile duct ligation, which is a common in vivo model used for the study of cholangiocyte proliferation and liver fibrosis. The proliferative response of cholangiocytes during cholestasis is regulated by the complex interaction of several factors, including gastrointestinal hormones, neuroendocrine hormones and autocrine or paracrine signalling mechanisms. Activation of biliary proliferation (ductular reaction) is thought to have a key role in the initiation and progression of liver fibrosis. The first part of this review provides an overview of the primary functions of cholangiocytes in terms of secretin-stimulated bicarbonate secretion – a functional index of cholangiocyte growth. In the second section, we explore the important regulators, both inhibitory and stimulatory, that regulate the cholangiocyte proliferative response during cholestasis. We discuss the role of proliferating cholangiocytes in the induction of fibrosis either directly via epithelial mesenchymal transition or indirectly via the activation of other liver cell types. The possibility of targeting cholangiocyte proliferation as potential therapy for reducing and/or preventing liver fibrosis, and future avenues for research into how cholangiocytes participate in the process of liver fibrogenesis are described.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 11 , July 2009 , e7
Copyright
Copyright © Cambridge University Press 2009

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References

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Further reading, resources and contacts

The American Association for the Study of Liver Disease (AASLD) website provides guidelines on the management of various liver diseases for professionals as well as numerous patient resources and links:

Alvaro, D. et al. (2007) Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver. Gastroenterology 132, 415-431CrossRefGoogle ScholarPubMed
Wallace, K., Burt, A. and Wright, M. (2008) Liver fibrosis. Biochemistry Journal 411, 1-18Google Scholar
Parola, M., Marra, F. and Pinzani, M. (2008) Myofibroblast-like cells and liver fibrogenesis: Emerging concepts in a rapidly moving scenario. Molecular Aspects of Medicine 29, 58-66Google Scholar
https://www.aasld.orgGoogle Scholar
http://www.liverfoundation.org/Google Scholar
Alvaro, D. et al. (2007) Proliferating cholangiocytes: a neuroendocrine compartment in the diseased liver. Gastroenterology 132, 415-431CrossRefGoogle ScholarPubMed
Wallace, K., Burt, A. and Wright, M. (2008) Liver fibrosis. Biochemistry Journal 411, 1-18Google Scholar
Parola, M., Marra, F. and Pinzani, M. (2008) Myofibroblast-like cells and liver fibrogenesis: Emerging concepts in a rapidly moving scenario. Molecular Aspects of Medicine 29, 58-66Google Scholar
https://www.aasld.orgGoogle Scholar
http://www.liverfoundation.org/Google Scholar