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Wound healing and local neuroendocrine regulation in the injured liver

Published online by Cambridge University Press:  29 April 2008

Mohammad R. Ebrahimkhani
Affiliation:
Cell signalling, Liver Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Ahmed M. Elsharkawy
Affiliation:
Cell signalling, Liver Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
Derek A. Mann*
Affiliation:
Cell signalling, Liver Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
*
*Corresponding author: Prof. Derek A. Mann, Liver Group, Institute of Cellular Medicine, 4th Floor, Cookson Building, Medical School, University of Newcastle, Newcastle upon Tyne, NE2 4HH, UK. Tel: +44 191 2223851; Fax: +44 191 2225455; E-mail: derek.mann@ncl.ac.uk

Abstract

The hepatic wound-healing response is a complex process involving many different cell types and factors. It leads to the formation of excessive matrix and a fibrotic scar, which ultimately disrupts proper functioning of the liver and establishes cirrhosis. Activated hepatic myofibroblasts, which are derived from cells such as hepatic stellate cells (HSCs), play a key role in this process. Upon chronic liver injury, there is an upregulation in the local neuroendocrine system and it has recently been demonstrated that activated HSCs express specific receptors and respond to different components of this system. Neuroendocrine factors and their receptors participate in a complex network that modulates liver inflammation and wound healing, and controls the development and progression of liver fibrosis. The first part of this review provides an overview of the molecular mechanisms governing hepatic wound healing. In the second section, we explore important components of the hepatic neuroendocrine system and their recently highlighted roles in HSC biology and hepatic fibrogenesis. We discuss the therapeutic interventions that are being developed for use in antifibrotic therapy.

Type
Review Article
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

The British Liver Trust website provides various resources for both patients and health professionals and includes links to other websites of interest:

Iredale, J.P. (2007) Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 117, 539-548CrossRefGoogle Scholar
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Weiskirchen, R. and Gressner, A.M. (2005) Isolation and culture of hepatic stellate cells. Methods Mol Med 117, 99-113Google ScholarPubMed
Mann, J. et al. (2007) Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Cell Death Differ 14, 275-285CrossRefGoogle ScholarPubMed
Iredale, J.P. (2007) Models of liver fibrosis: exploring the dynamic nature of inflammation and repair in a solid organ. J Clin Invest 117, 539-548CrossRefGoogle Scholar
Friedman, S.L. and Bansal, M.B. (2006) Reversal of hepatic fibrosis – fact or fantasy? Hepatology 43, S82-S88CrossRefGoogle ScholarPubMed
Weiskirchen, R. and Gressner, A.M. (2005) Isolation and culture of hepatic stellate cells. Methods Mol Med 117, 99-113Google ScholarPubMed
Mann, J. et al. (2007) Regulation of myofibroblast transdifferentiation by DNA methylation and MeCP2: implications for wound healing and fibrogenesis. Cell Death Differ 14, 275-285CrossRefGoogle ScholarPubMed