Modulation of stellate cell proliferation and gene expression by rat hepatocytes: effect of toxic iron overload

被引：15

作者：

Parkes, JG ^{[1
]}

Templeton, DM ^{[1
]}

机构：

[1] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada

来源：

TOXICOLOGY LETTERS | 2003年 / 144卷 / 02期

基金：

加拿大健康研究院;

关键词：

iron overload; hepatocyte; hepatic stellate cell; fibrosis; collagen; TGF-beta;

D O I：

10.1016/S0378-4274(03)00222-4

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 ;

摘要：

Mechanisms by which hepatocytes and transdifferentiated hepatic stellate cells (HSC) initiate liver fibrosis in chronic iron toxicity are unknown. This study was to determine if factors in media from control and iron-loaded rat hepatocyte cultures modulate HSC gene expression and proliferation. Conditioned medium (CM) from both control and iron-loaded hepatocytes increased serum-stimulated DNA synthesis by HSC to 140% of control values (P < 0.05). Heating CM (15 min, 80 degreesC) caused a suppression of DNA synthesis that was partially reversed by a TGF-beta-neutralizing antibody. Addition of TGF-beta(1), reproduced the suppression. Levels in HSC of mRNA for collagen type 1, collagen type IV. TGF-beta, and plasminogen activator inhibitor-1 were unaffected by exposure to CM but increased significantly when CM from iron-loaded hepatocytes was heat-treated. In HepG2 cell cultures, iron loading increased total (but not activated) TGF-beta secretion into the medium approximately 2-fold. We conclude that increased secretion of latent TGF-beta by hepatocytes injured by iron is a potential factor influencing fibrogenic behavior of HSC. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

引用

页码：225 / 233

页数：9

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