A role for serotonin (5-HT) in hepatic stellate cell function and liver fibrosis

Ruddell, Richard G., Oakley, Fiona, Hussain, Ziafat, Yeung, Irene, Bryan-Lluka, Lesley J., Ramm, Grant A. and Mann, Derek A. (2006) A role for serotonin (5-HT) in hepatic stellate cell function and liver fibrosis. American Journal Of Pathology, 169 3: 861-876.


Author Ruddell, Richard G.
Oakley, Fiona
Hussain, Ziafat
Yeung, Irene
Bryan-Lluka, Lesley J.
Ramm, Grant A.
Mann, Derek A.
Title A role for serotonin (5-HT) in hepatic stellate cell function and liver fibrosis
Journal name American Journal Of Pathology   Check publisher's open access policy
ISSN 0002-9440
1525-2191
0097-3599
Publication date 2006-09
Sub-type Article (original research)
DOI 10.2353/ajpath.2006.050767
Volume 169
Issue 3
Start page 861
End page 876
Total pages 16
Editor Jay M. McDonald
Maria Eisemann
Place of publication Bethesda, MD, U.S.A.
Publisher American Society for Investigative Pathology
Collection year 2006
Language eng
Subject C1
Formatted abstract Hepatic stellate cells (HSCs) are key cellular components of hepatic wound healing and fibrosis. There is emerging evidence that the fibrogenic function of HSCs may be influenced by neurochemical and neurotrophic factors. This study addresses the potential for the serotonin (5-HT) system to influence HSC biology. Rat and human HSCs express the 5-HT1B, 5-HT1F 5-HT2A 5-HT2B, and 5-HT7 receptors, with expression of 5-HT1B 5-HT2A and 5-HT2B being induced on HSC activation. Induction of 5-HT2A and 5-HT2B was 106 ± 39- and 52 ± 8.5-fold that of quiescent cells, respectively. 5-HT2B was strongly associated with fibrotic tissue in diseased rat liver. Treatment of HSCs with 5-HT2 antagonists suppressed proliferation and elevated their rate of apoptosis; by contrast 5-HT was protective against nerve growth factor-induced apoptosis. 5-HT synergized with platelet-derived growth factor to stimulate increased HSC proliferation. HSCs were shown to express a functional serotonin transporter and to participate in both active uptake and release of 5-HT. We conclude that HSCs express key regulatory components of the 5-HT system enabling them to store and release 5-HT and to respond to the neurotransmitter in a profibrogenic manner. Antagonists that selectively target the 5-HT class of receptors may be exploited as antifibrotic drugs.
Copyright © American Society for Investigative Pathology
Keyword Pathology
Growth-factor
Mesangial Cells
Extracellular-matrix
Gene-expression
Igf-i
Transporter
Apoptosis
Receptor
Activation
Induction
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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Created: Wed, 15 Aug 2007, 08:18:50 EST