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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