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• W2064465196 abstract "<b>Background and aim:</b> Significant telomere shortening of hepatocytes is associated with replicative senescence and a non-dividing state in chronic liver disease, resulting in end stage liver failure and/or development of hepatocellular carcinoma. To prevent critical telomere shortening in hepatocytes, we have focused on oestrogen dependent transactivation of the human telomerase reverse transcriptase (<i>hTERT</i>) gene as a form of telomerase therapy in chronic liver disease. <b>Methods:</b> We examined expression of <i>hTERT</i> mRNA and its protein, and telomerase activity (TA) in three human normal hepatic cell lines (Hc-cells, h-Nheps, and WRL-68) before and after treatment with 17β-oestradiol. The effects of exogenous oestradiol administration were examined in a carbon tetrachloride (CCl₄) induced model of liver fibrosis in rats. <b>Results:</b> Expression of <i>hTERT</i> mRNA and its protein was upregulated by oestradiol treatment. Telomere length decreased in Hc-cells and h-Nheps with accumulated passages whereas with long term oestradiol exposure it was greater than without oestradiol. The incidence of β-galactosidase positive cells, indicating a state of senescence, decreased significantly in oestradiol treated cells in comparison with non-treated cells (p<0.05). TA in both male and female rats with CCl₄ induced liver fibrosis was significantly higher with oestradiol administration than without (p<0.05). Long term oestradiol administration markedly rescued the hepatic telomere from extensive shortening in both male and female rats. <b>Conclusion:</b> These results suggest that oestradiol acts as a positive modulator of the <i>hTERT</i> gene in the liver. Oestrogen dependent transactivation of the <i>hTERT</i> gene is a new strategy for slowing the progression of chronic liver disease." @default.
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• W2064465196 date "2004-07-01" @default.
• W2064465196 modified "2023-09-22" @default.
• W2064465196 title "Prevention of critical telomere shortening by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis" @default.
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• W2064465196 doi "https://doi.org/10.1136/gut.2003.027516" @default.
• W2064465196 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1774098" @default.
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