Effects of retinol and hepatocyte-conditioned medium on cultured rat hepatic stellate cells.
Hepatic stellate cells (HSC) become activated in liver injury, proliferating and secreting components of connective tissue. Activated HSC lose their native retinol and fat storing capacity. Signals from hepatocytes and/or Kupffer cells injured (eg, by iron overload) may contribute to the so-called activated HSC phenotype. Primary rat HSC cultures were treated with retinol to determine if this could produce a quiescent cell for controlled in vitro studies of activation. Retinol resulted in suppressed DNA synthesis in proliferating HSC, a reorganization of actin filaments, and a return of fat storage. However, it did not suppress the expression of fibrogenic genes such as those for collagens type I and IV, and TGF-beta1. Furthermore, retinol-treated cells may increase expression of these genes in response to conditioned medium from hepatocyte cultures. The effect is especially apparent for collagen type I mRNA, and with conditioned medium from iron-loaded hepatocytes. Thus, retinol may be a two-edged sword in iron overload, potentially suppressing HSC proliferation on the one hand, and sensitizing a fibrogenic pattern of gene expression on the other. Factors influencing this balance merit further study.
Parkes
Joel G
JG
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
Templeton
Douglas M
DM
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024141:Collagen Type IV / Q000378:metabolism; D017077:Culture Media, Conditioned; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000378:metabolism*; D019190:Iron Overload / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014801:Vitamin A / Q000494:pharmacology*
D024042:Collagen Type I; D024141:Collagen Type IV; D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D014801:Vitamin A; D004247:DNA