{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:11:44Z","timestamp":1790050304327,"version":"4.0.1"},"reference-count":54,"publisher":"BMJ","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[2004,7]]},"abstract":"<jats:p>\n                    <jats:bold>Background and aim:<\/jats:bold>\n                    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 (\n                    <jats:italic>hTERT<\/jats:italic>\n                    ) gene as a form of telomerase therapy in chronic liver disease.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We examined expression of\n                    <jats:italic>hTERT<\/jats:italic>\n                    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 17\u03b2-oestradiol. The effects of exogenous oestradiol administration were examined in a carbon tetrachloride (CCl\n                    <jats:sub>4<\/jats:sub>\n                    ) induced model of liver fibrosis in rats.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Expression of\n                    <jats:italic>hTERT<\/jats:italic>\n                    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 \u03b2-galactosidase positive cells, indicating a state of senescence, decreased significantly in oestradiol treated cells in comparison with non-treated cells (p&lt;0.05). TA in both male and female rats with CCl\n                    <jats:sub>4<\/jats:sub>\n                    induced liver fibrosis was significantly higher with oestradiol administration than without (p&lt;0.05). Long term oestradiol administration markedly rescued the hepatic telomere from extensive shortening in both male and female rats.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    These results suggest that oestradiol acts as a positive modulator of the\n                    <jats:italic>hTERT<\/jats:italic>\n                    gene in the liver. Oestrogen dependent transactivation of the\n                    <jats:italic>hTERT<\/jats:italic>\n                    gene is a new strategy for slowing the progression of chronic liver disease.\n                  <\/jats:p>","DOI":"10.1136\/gut.2003.027516","type":"journal-article","created":{"date-parts":[[2004,6,11]],"date-time":"2004-06-11T23:18:02Z","timestamp":1086995882000},"page":"1001-1009","source":"Crossref","is-referenced-by-count":42,"title":["Prevention of critical telomere shortening by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis"],"prefix":"10.1136","volume":"53","author":[{"given":"R","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Maesawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Fujisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Oikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y","family":"Takikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Oikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Ishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2004,6,11]]},"reference":[{"key":"2025090723004681000_53.7.1001.1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.01-0977com"},{"key":"2025090723004681000_53.7.1001.2","unstructured":"Rudolph KL, Depinho RA. Telomeres and telomerase in experimetal liver cirrhosis. In: Arias IM, Boyer JL, Chisari FV, et al, eds. The liver: biology and pathobiology. 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