Fibroproliferative activation of ito cells in experimental
alcoholic liver fibrosis.
Tsukamoto, Hidekazu, Steve Cheng, and William S. Blaner.
Department of Medicine, MetroHealth Medical Center and Department
of Veterans Affairs Medical Center, Case Western Reserve University,
Cleveland, Ohio 44109; Children's Hospital in Oakland Research
Institute, Oakland, CA; and Institute of Human Nutrition, College of
Physicians and Surgeons of Columbia University, New York, New
York
APStracts 2:0017G, 1995. - WITHDRAWN
Ito cells, vitamin A-storing, perisinusoidal cells, are believed to
undergo fibroproliferative activation in liver fibrogenesis. In the
present study, we have tested this hypothesis in Ito cells isolated
from early and advanced stages of experimental alcoholic liver
fibrosis in rats by examining their vitamin A content, DNA synthesis
and gene expression of procollagen [alpha]I(I) (COLL), transforming growth
factor [beta]1 (TGF[beta]1) and smooth muscle [alpha]-actin ([alpha]-SM). In
the early fibrosis, the content of retinyl palmitate (RP) and cellular retinol
binding protein in Ito cells were already reduced to 17% and 33% of
those in the control rats. Ito cell DNA synthesis determined ex vivo
was markedly enhanced 3-fold. Collagen production measured ex vivo was
increased only by 40%, and the COLL mRNA level in the freshly
isolated cells examined by Northern blot analysis, showed a moderate
elevation. At the advanced stage, the RP content continued to be
depleted, and ex vivo DNA synthesis enhanced by the similar magnitude.
However, the enhancement of ex vivo collagen production and in vivo
COLL mRNA expression were clearly accentuated by 2.8 and 18.4 fold.
Furthermore, mRNA levels of TGF[beta]1 and [alpha]-SM in these cells were also
increased 2.8 and 2.3 fold, respectively while such induction was not
detected in the early fibrosis. These results demonstrate the two
phases of Ito cell activation in this experimental model which are
characterized as the early proliferative response with marked vitamin
A depletion and the late fibrogenic activation with induction of
collagen, TGF[beta]1 and [alpha]-SM genes.
Received 15 June 1994; accepted in final form 3 January 1995.
APS Manuscript Number G233-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.