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Sympathetic nervous system inhibition increases hepatic progenitors and reduces liver injury.

Publication ,  Journal Article
Oben, JA; Roskams, T; Yang, S; Lin, H; Sinelli, N; Li, Z; Torbenson, M; Huang, J; Guarino, P; Kafrouni, M; Diehl, AM
Published in: Hepatology
September 2003

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.

Duke Scholars

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Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

September 2003

Volume

38

Issue

3

Start / End Page

664 / 673

Location

United States

Related Subject Headings

  • Transaminases
  • Sympathetic Nervous System
  • Sympathectomy, Chemical
  • Stem Cells
  • Prazosin
  • Oxidopamine
  • Organ Size
  • Neural Inhibition
  • Necrosis
  • Mice, Inbred C57BL
 

Citation

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Oben, J. A., Roskams, T., Yang, S., Lin, H., Sinelli, N., Li, Z., … Diehl, A. M. (2003). Sympathetic nervous system inhibition increases hepatic progenitors and reduces liver injury. Hepatology, 38(3), 664–673. https://doi.org/10.1053/jhep.2003.50371
Oben, Jude A., Tania Roskams, Shiqi Yang, Huizhi Lin, Nicoletta Sinelli, Zhiping Li, Michael Torbenson, et al. “Sympathetic nervous system inhibition increases hepatic progenitors and reduces liver injury.Hepatology 38, no. 3 (September 2003): 664–73. https://doi.org/10.1053/jhep.2003.50371.
Oben JA, Roskams T, Yang S, Lin H, Sinelli N, Li Z, et al. Sympathetic nervous system inhibition increases hepatic progenitors and reduces liver injury. Hepatology. 2003 Sep;38(3):664–73.
Oben, Jude A., et al. “Sympathetic nervous system inhibition increases hepatic progenitors and reduces liver injury.Hepatology, vol. 38, no. 3, Sept. 2003, pp. 664–73. Pubmed, doi:10.1053/jhep.2003.50371.
Oben JA, Roskams T, Yang S, Lin H, Sinelli N, Li Z, Torbenson M, Huang J, Guarino P, Kafrouni M, Diehl AM. Sympathetic nervous system inhibition increases hepatic progenitors and reduces liver injury. Hepatology. 2003 Sep;38(3):664–673.
Journal cover image

Published In

Hepatology

DOI

ISSN

0270-9139

Publication Date

September 2003

Volume

38

Issue

3

Start / End Page

664 / 673

Location

United States

Related Subject Headings

  • Transaminases
  • Sympathetic Nervous System
  • Sympathectomy, Chemical
  • Stem Cells
  • Prazosin
  • Oxidopamine
  • Organ Size
  • Neural Inhibition
  • Necrosis
  • Mice, Inbred C57BL