AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 6 1090-G1095, Copyright © 1993 by American Physiological Society
Posttranslational inhibition of Ito cell type I collagen production by triiodothyronine
T. W. Lissoos, D. W. Beno and B. H. Davis
Department of Medicine, University of Chicago, Illinois 60637.
Increased Ito cell collagen production occurs during in vivo liver
fibrogenesis. Regulation of the overproduction of collagen was studied in
cultured rat hepatic Ito cells, which resemble the myofibroblast associated
with liver fibrosis. Previous studies suggest that the steroid hormones,
retinoic acid, and glucocorticoids may have antifibrogenic properties in
vitro and in vivo when used at pharmacological doses. Their potential roles
at physiological levels are not well understood. The current study examined
the potential regulation of the overproduction of type I collagen in
cultured rat hepatic Ito cells by another steroid hormone,
3,5,3'-triiodo-L-thyronine (T3). T3 induced a 3.4-fold reduction in type I
collagen production. The effect was dose dependent and was maximal with
physiological levels of T3 (10(-9) M). The effect of T3 was independent of
any suppression in total protein synthesis. The mechanism of the
suppressive effect of T3 on collagen production was explored and was found
to be at a posttranslational level. This study suggests that the inhibitory
effects of T3 on type I collagen production are likely caused by enhanced
intracellular turnover of type I collagen.
