Modulation of vitamin A metabolism during hepatic and intestinal cell culture

Abstract

Vitamin A metabolism was studied in vitro, contrasting primary cultures of hepatocytes, passaged cultures of Ito cells (non-parenchymal fat-storing hepatic cells) and IEC-6 intestinal crypt cells. The regulation of the retinyl esterification process, the central process in vitamin A storage, was evaluated. The potential influence of variations in the cell's surrounding extracellular collagen millieu was considered by growing the cells on either a type I collagen matrix, a type IV collagen matrix or a basement membrane-like matrix. The various matrices were used to stimulate changes in the extracellular collagen millieu which may occur during various fibrogenic states. In addition, the co-modulating influence of transforming growth factor beta (TGF beta) was considered since this ubiquitous peptide may be prominently involved in tissue fibrosis, a process which may be associated with alterations in intracellular vitamin A. It was found that each cell type had its own characteristic response to the various collagen surfaces and TGF beta. There was a reduction in retinyl esterification when the hepatic cells were grown on a type I collagen matrix in the presence of TGF beta which might simulate a 'fibrogenic' environment. This did not appear to be due to changes in retinyl ester stability. The TGF beta response may be somewhat cell specific, since TGF beta exposure increased the amount of retinyl esterification in the intestinal cell line. These studies suggest that vitamin A storage may be affected by changes in the surrounding extracellular matrix and by soluble cytokine mediators.