title: Effects of retinol and hepatocyte-conditioned medium on cultured rat hepatic stellate cells.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Joel G
authors.initials: JG
authors.lastname: Parkes
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Templeton
mesh_terms: 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*
chemical_list: D024042:Collagen Type I; D024141:Collagen Type IV; D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D014801:Vitamin A; D004247:DNA