a1 Cell signalling, Liver Group, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
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.
c1 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: [email protected]