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Sympathetic nervous system regulation of liver repair.

Oben, JA; Diehl, AM; (2004) Sympathetic nervous system regulation of liver repair. Anat Rec A Discov Mol Cell Evol Biol , 280 (1) pp. 874-883. 10.1002/ar.a.20081.

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This chapter reviews recent evidence that the sympathetic nervous system (SNS) regulates liver repair by modulating the phenotypes of hepatic stellate cells (HSCs), the liver's principal fibrogenic cells, and hepatic epithelial progenitors, i.e., oval cells. SNS nerve fibers touch HSCs and these cells express adrenoceptors, suggesting that HSCs may be targets for SNS neurotransmitters. HSCs also contain catecholamine biosynthetic enzymes, release norepinephrine (NE), and are growth-inhibited by adrenoceptor antagonists. In addition, HSCs from mice with reduced levels of NE grow poorly in culture and exhibit inhibited activation during liver injury. Finally, growth and injury-related fibrogenic responses are rescued by adrenoceptor agonists. Thus, certain SNS inhibitors (SNSIs) protect experimental animals from cirrhosis. Conversely, SNSIs enhance the hepatic accumulation of oval cells (OCs) in injured livers. This response is associated with improved liver injury. Because SNSIs do not affect the expression of cytokines, growth factors, or growth factor receptors that are known to regulate OCs, and OCs express adrenoceptors, it is conceivable that catecholamines influence OCs by direct interaction with OC adrenoceptors. Given evidence that the SNS regulates the viability and activation of HSCs and OCs differentially, SNSIs may be novel therapies to improve the repair of damaged livers.

Type: Article
Title: Sympathetic nervous system regulation of liver repair.
Location: United States
DOI: 10.1002/ar.a.20081
Keywords: Acetylcholine, Animals, Epithelial Cells, Humans, Leptin, Liver, Liver Cirrhosis, Mice, Neuropeptide Y, Neurotransmitter Uptake Inhibitors, Norepinephrine, Sympathetic Nervous System
UCL classification: UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/41541
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