AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 1 157-G162, Copyright © 1993 by American Physiological Society
Lipocytes from fibrotic rat liver have an impaired feedback response to procollagen propeptides
H. Ikeda, G. Y. Wu and C. H. Wu
Department of Medicine, University of Connecticut School of Medicine, Farmington 06030.
Procollagen propeptides have been previously shown to be taken up by
cultured fibroblasts and to inhibit collagen production at translational
and transcriptional levels. In hepatic fibrosis, Ito cells are thought to
be major contributors to collagen overproduction. We wondered whether an
impaired response to procollagen propeptides by Ito cells from fibrotic
liver could be a mechanism involved in collagen overproduction in hepatic
fibrosis. In the presence of type I procollagen carboxy-terminal propeptide
(200 nM), collagen production by Ito cells from normal rats was
significantly decreased to 62.0% of control, whereas collagen production by
Ito cells from two models of hepatic fibrosis in the rat, bile duct
ligation and carbon tetrachloride treatment, was not significantly changed
(102.4 and 102.6% of controls, respectively). By measurement of type I
procollagen mRNA levels, this difference in response to procollagen
carboxy-terminal propeptide was determined to occur at a pretranslational
level. The rates of uptake, transfer to the nuclear compartment, and
degradation of procollagen propeptide were not significantly different in
Ito cells from normal and fibrotic liver.
