Sympathetic nervous system inhibition increases hepatic progenitors and reduces liver injury.
Recovery from liver damage might be enhanced by encouraging repopulation of the liver by endogenous hepatic progenitor cells. Oval cells are resident hepatic stem cells that promote liver regeneration and repair. Little is known about the mediators that regulate the accumulation of these cells in the liver. Parasympathetic nervous system inhibition reduces the number of oval cells in injured livers. The effect of sympathetic nervous system (SNS) inhibition on oval cell number is not known. Adrenergic inhibition mobilizes hematopoietic precursors into the circulation and has also been shown to promote liver regeneration. Thus, we hypothesized that SNS inhibition would promote hepatic accumulation of oval cells and reduce liver damage in mice fed antioxidant-depleted diets to induce liver injury. Our results confirm this hypothesis. Compared with control mice that were fed only the antioxidant-depleted diets, mice fed the same diets with prazosin (PRZ, an alpha-1 adrenoceptor antagonist) or 6-hydroxydopamine (6-OHDA, an agent that induces chemical sympathectomy) had significantly increased numbers of oval cells. Increased oval cell accumulation was accompanied by less hepatic necrosis and steatosis, lower serum aminotransferases, and greater liver and whole body weights. Neither PRZ nor 6-OHDA affected the expression of cytokines, growth factors, or growth factor receptors that are known to regulate progenitor cells. In conclusion, stress-related sympathetic activity modulates progenitor cell accumulation in damaged livers and SNS blockade with alpha-adrenoceptor antagonists enhances hepatic progenitor cell accumulation.
Oben
Jude A
JA
Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Roskams
Tania
T
Yang
Shiqi
S
Lin
Huizhi
H
Sinelli
Nicoletta
N
Li
Zhiping
Z
Torbenson
Michael
M
Huang
Jiawen
J
Guarino
Paul
P
Kafrouni
Michel
M
Diehl
Anna Mae
AM
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001835:Body Weight; D004032:Diet; D005234:Fatty Liver / Q000517:prevention & control; D022781:Hepatocytes / Q000473:pathology*; D008099:Liver / Q000473:pathology*; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis; D009433:Neural Inhibition; D009929:Organ Size; D016627:Oxidopamine / Q000008:administration & dosage; D011224:Prazosin / Q000008:administration & dosage; D013234:Stem Cells / Q000473:pathology*; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D000637:Transaminases / Q000097:blood
D000317:Adrenergic alpha-Antagonists; D000975:Antioxidants; D016627:Oxidopamine; D000637:Transaminases; D011224:Prazosin