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  • Title: TGF-beta and collagen-alpha 1 (I) gene expression are increased in hepatic acinar zone 1 of rats with iron overload.
    Author: Houglum K, Bedossa P, Chojkier M.
    Journal: Am J Physiol; 1994 Nov; 267(5 Pt 1):G908-13. PubMed ID: 7977754.
    Abstract:
    We have shown that lipid peroxidation stimulates collagen-alpha 1 (I) gene transcription in cultured cells. Because iron is a transitional metal known to induce lipid peroxidation, we investigated whether hepatic lipid peroxidation modulates collagen gene expression in iron-overloaded rats. In this animal model of hemochromatosis, we show colocalization with iron in the hepatic acinar zone 1 of both lipid peroxidation and increased collagen-alpha 1 (I) transcripts, using immunohistochemistry for malondialdehyde-protein adducts and in situ hybridization, respectively. Iron overload stimulated the expression of the cytokine transforming growth factor-beta (TGF-beta) in acinar zone 1, in spite of the minor degree of hepatocellular necrosis and inflammation. The formation of reactive aldehydes and TGF-beta, both inducers of collagen gene expression, may play a role in the stimulation of hepatic collagen production in iron overload. These mechanisms could be a link between iron overload and fibrosis in genetic hemochromatosis.
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