Lipocytes from fibrotic rat liver have an impaired feedback response to procollagen propeptides

Abstract

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.