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From the Divisions of Cell and Molecular Medicine and Cancer
Sciences,*
University of Southampton, Southampton General
Hospital, Southampton; and the Liver Centre
Laboratories,
Queen Elizabeth Hospital,
Edgbaston, Birmingham, United Kingdom
We have examined the expression of p75, a member of the TNF
receptor superfamily in hepatic stellate cells (HSC) and pancreatic
stellate cells (PSC). Activated HSC and PSC were demonstrated by
Western blot analysis to express p75. p75 was immunolocalized to cells
with a myofibroblast-like morphology in the fibrotic bands of six
fibrotic and cirrhotic liver biopsies and three biopsies of fibrotic
human pancreas. Immunostaining of parallel sections indicated that
these cells were 
-smooth muscle actin-positive, identifying
them as activated HSC and PSC, respectively. HSC apoptosis in
tissue culture in the presence of serum was quantified after addition
of 0.1 to 100 ng/ml of nerve growth factor (NGF) a ligand for
p75, by in situ counting of apoptotic bodies
after addition of acridine orange. HSC demonstrated a significant
increase in apoptosis in response to 100 ng/ml NGF (0.05 >
P by Wilcoxon’s rank; n = 7) after
24 hours. NGF 100 ng/ml had no effect on HSC proliferation, but
reduced total HSC DNA by 19% relative to control after 24 hours
(n = 3). These data demonstrate that activated HSC
express p75 and respond to NGF stimulation by undergoing apoptosis. We
therefore report p75 as a novel marker of activated HSC and suggest
that signaling via ligand binding to p75 may provide a mechanism for
selective apoptosis of HSC.
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