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Inhibitory effect of oestradiol on activation of rat hepatic stellate cells in vivo and in vitro
  1. I Shimizua,
  2. Y Mizobuchia,
  3. M Yasudaa,
  4. M Shibaa,
  5. Y-R Mab,
  6. T Horiea,
  7. F Liua,
  8. S Itoa
  1. aSecond Department of Internal Medicine, School of Medicine, University of Tokushima, Tokushima, Japan, bDepartment of Preclinical Medicine, Luzhou Medical College, Luzhou, China
  1. Dr I Shimizu, Second Department of Internal Medicine, Tokushima University School of Medicine, Kuramoto-cho, Tokushima 770-8503, Japan.

Abstract

Background Hepatic stellate cells play a key role in the pathogenesis of hepatic fibrosis.

Aims To examine the inhibitory effect of oestradiol on stellate cell activation.

Methods In vivo, hepatic fibrosis was induced in rats by dimethylnitrosamine or pig serum. In vitro, rat stellate cells were activated by contact with plastic dishes resulting in their transformation into myofibroblast-like cells.

Results In the dimethylnitrosamine and pig serum models, treatment with oestradiol at gestation related doses resulted in a dose dependent suppression of hepatic fibrosis with restored content of hepatic retinyl palmitate, reduced collagen content, lower areas of stellate cells which express α smooth muscle actin (α-SMA) and desmin, and lower procollagen type I and III mRNA levels in the liver. In cultured stellate cells, oestradiol inhibited type I collagen production, α-SMA expression, and cell proliferation. These findings suggest that oestradiol is a potent inhibitor of stellate cell transformation.

Conclusion The antifibrogenic role of oestradiol in the liver may contribute to the sex associated differences in the progression from hepatic fibrosis to cirrhosis.

  • hepatic stellate cells
  • hepatic fibrosis
  • oestradiol
  • α smooth muscle actin
  • retinyl palmitate
  • Abbreviations

    SMA
    smooth muscle actin
    ECM
    extracellular matrix
    DMN
    dimethylnitrosamine
    PS
    pig serum
    RP
    reinyl palmitate
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    SDS
    sodium dodecyl sulphate
    DMEM
    Dulbecco’s modified Eagle’s Medium
    FBS
    fetal bovine serum
    HRP
    horseradish peroxidase
    PBS
    phosphate buffered saline
    BrdU
    bromodeoxyuridine
    TGF
    transforming growth factor
    PDGF
    platelet derived growth factor
    IFN
    interferon
    MDA
    malondialdehyde
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  • Abbreviations

    SMA
    smooth muscle actin
    ECM
    extracellular matrix
    DMN
    dimethylnitrosamine
    PS
    pig serum
    RP
    reinyl palmitate
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    SDS
    sodium dodecyl sulphate
    DMEM
    Dulbecco’s modified Eagle’s Medium
    FBS
    fetal bovine serum
    HRP
    horseradish peroxidase
    PBS
    phosphate buffered saline
    BrdU
    bromodeoxyuridine
    TGF
    transforming growth factor
    PDGF
    platelet derived growth factor
    IFN
    interferon
    MDA
    malondialdehyde
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