Acetylcholine promotes the proliferation and collagen gene expression of myofibroblastic hepatic stellate cells.
The mechanisms that initiate and perpetuate the fibrogenic response, during liver injury, are unclear. Animal studies, however, strongly support a role for the autonomic nervous system (ANS) in wound healing. Therefore, the ANS may also mediate the development of cirrhosis. Hepatic stellate cells (HSC), the liver's major matrix-producing cells, are activated by injury to become proliferative, fibrogenic myofibroblasts. HSC respond to sympathetic neurotransmitters by changing phenotype, suggesting that HSC may be the cellular effectors of ANS signals that modulate hepatic fibrogenesis during recovery from liver damage. We show here that the parasympathetic neurotransmitter acetylcholine markedly stimulates the proliferation of myofibroblastic HSC and induces HSC collagen gene expression in these cells. By extending evidence that HSC are direct targets of the ANS, these results support the proposed neuroglial role of HSC in the liver and suggest that interrupting ANS signalling may be useful in constraining the fibrogenic response to liver injury.
Oben
Jude A
JA
Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, 912 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21286, USA.
Yang
Shiqi
S
Lin
Huizhi
H
Ono
Mafasumi
M
Diehl
Anna Mae
AM
D000109:Acetylcholine / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001341:Autonomic Nervous System / Q000503:physiopathology; D002455:Cell Division / Q000187:drug effects; D003094:Collagen / Q000235:genetics*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology* / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL
D003094:Collagen; D000109:Acetylcholine