Sympathetic nervous system regulation of liver repair
Article first published online: 3 SEP 2004
Copyright © 2004 Wiley-Liss, Inc.
The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology
Special Issue: The Hepatic Nervous System
Volume 280A, Issue 1, pages 874–883, September 2004
How to Cite
Oben, J. A. and Diehl, A. M. (2004), Sympathetic nervous system regulation of liver repair. Anat. Rec., 280A: 874–883. doi: 10.1002/ar.a.20081
- Issue published online: 20 SEP 2004
- Article first published online: 3 SEP 2004
- Manuscript Accepted: 20 JUN 2004
- Manuscript Received: 11 MAR 2004
- hepatic oval cells;
- hepatic stellate cells;
- liver regeneration
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. © 2004 Wiley-Liss, Inc.