Norepinephrine and neuropeptide Y promote proliferation and collagen gene expression of hepatic myofibroblastic stellate cells.

Published

Journal Article

The mechanisms initiating and perpetuating the fibrogenic response in the injured liver are not well understood. Hepatic stellate cells are activated by liver injury to become proliferative and fibrogenic myofibroblasts. Emerging evidence suggests that the sympathetic nervous system may play a role in the development of cirrhosis. It is not known, however, whether this requires a direct interaction between sympathetic neurotransmitters and stellate cell receptors, or results indirectly, from sympathetic effects on the vasculature. Using cultured hepatic stellate cells, we show that the sympathetic neurotransmitters, norepinephrine and neuropeptide Y, markedly stimulate the proliferation of activated, myofibroblastic, hepatic stellate cells. Norepinephrine, but not neuropeptide Y, also induces collagen gene expression. In conclusion, physiologically relevant concentrations of sympathetic neurotransmitters directly modulate the phenotype of hepatic stellate cells. This suggests that targeted interruption of sympathetic nervous system signaling in hepatic stellate cells may be useful in constraining the fibrogenic response to liver injury.

Full Text

Duke Authors

Cited Authors

  • Oben, JA; Yang, S; Lin, H; Ono, M; Diehl, AM

Published Date

  • March 2003

Published In

Volume / Issue

  • 302 / 4

Start / End Page

  • 685 - 690

PubMed ID

  • 12646223

Pubmed Central ID

  • 12646223

Electronic International Standard Serial Number (EISSN)

  • 1090-2104

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/s0006-291x(03)00232-8

Language

  • eng