Posttranslational inhibition of Ito cell type I collagen production by triiodothyronine
Lissoos, T.W.; Beno, D.W.; Davis, B.H.
American Journal of Physiology 264(6 Pt 1): G1090-G1095
1993
ISSN/ISBN: 0002-9513 PMID: 8333536 Document Number: 421876
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 (T-3). T-3 induced a 3.4-fold reduction in type I collagen production. The effect was dose dependent and was maximal with physiological levels of T-3 (10-9 M). The effect of T-3 was independent of any suppression in total protein synthesis. The mechanism of the suppressive effect of T-3 on collagen production was explored and was found to be at a posttranslational level. This study suggests that the inhibitory effects of T-3 on type I collagen production are likely caused by enhanced intracellular turnover of type I collagen.