TNF-α regulates mouse fetal hepatic maturation induced by oncostatin M and extracellular matrices

Authors

  • Akihide Kamiya,

    1. Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD
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  • Frank J. Gonzalez

    Corresponding author
    1. Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD
    • Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Building 37, Room 3106B, 9000 Rockville Pike, Bethesda, MD 20892
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    • fax: 301-496-8419


Abstract

Fetal hepatic maturation consists of multisteps and is regulated by several cytokines and cell–cell or cell–matrices interactions. In the mid-to-late fetal stage, hepatocytes have few metabolic functions associated with adult liver homeostasis. Cultured fetal hepatocytes acquire the expression of several mature liver-specific genes through stimulation with hepatic maturation factor oncostatin M (OSM) and matrigel. Tumor necrosis factor-α (TNFα) regulates fetal hepatic maturation stimulated by OSM and matrigel. TNFα suppressed expression of mature liver-specific genes such as tyrosine aminotransferase and apolipoproteins. In addition, the expression of hematopoietic cytokines and cyclin A2, repressed by OSM and matrigel, is induced by TNFα in the fetal hepatic cultures coincident with cell division. TNFα inhibited the induction of hepatocyte nuclear factor 4α induced by OSM and matrigel, suggesting that down-regulation of hepatocyte nuclear factor 4α expression is involved in the mechanism of suppression of hepatic maturation by TNFα. Interestingly, TNFα is expressed in the prenatal and postnatal liver but not in adult liver, whereas TNFR1, a TNFα receptor, is expressed in both fetal and adult livers. In conclusion, TNFα is a suppressive factor of hepatic maturation. The balance between hepatic maturation factor (OSM and extracellular matrices) and TNFα is important for liver development. (HEPATOLOGY 2004;40:527–536.)

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