ArticleGut2004
Prevention of critical telomere shortening by oestradiol in human normal hepatic cultured cells and carbon tetrachloride induced rat liver fibrosis.
Article in Gut, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 49 citations in OpenAlex.
- Associations of Accelerated DNA Methylation Aging Algorithms with Chronic Liver Disease and All-Cause Mortality.Biomedicines · 2026Article
- Synergistic senolytic-regenerative therapy significantly extends healthspan and lifespan.Journal of translational medicine · 2026Article
- Aging reduces liver resiliency by dysregulating Hedgehog signaling.Aging cell · 2022Article
- Relation between sex hormones and leucocyte telomere length in men with idiopathic pulmonary fibrosis.Respirology (Carlton, Vic.) · 2020Article
- The effects of transplanted mesenchymal stem cells treated with 17-b estradiol on experimental autoimmune encephalomyelitis.Molecular biology reports · 2019Article
- Article
- Validation of quantitative polymerase chain reaction with Southern blot method for telomere length analysis.Future science OA · 2018Article
- Lipopolysaccharide induces the differentiation of hepatic progenitor cells into myofibroblasts via activation of the Hedgehog signaling pathway.Cell cycle (Georgetown, Tex.) · 2017Article
- Enhanced sedative efficacy and delayed recovery in propofol anesthesia in a rat model of hepatic cirrhosis.International journal of clinical and experimental medicine · 2015Article
- Impact of lifetime opioid exposure on arterial stiffness and vascular age: cross-sectional and longitudinal studies in men and women.BMJ open · 2014Article
- Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study.Human reproduction (Oxford, England) · 2012Article
- The effects of 17-β estradiol on enhancing proliferation of human bone marrow mesenchymal stromal cells in vitro.Stem cells and development · 2011Article
- Can meditation slow rate of cellular aging? Cognitive stress, mindfulness, and telomeres.Annals of the New York Academy of Sciences · 2009Review
- Role of sex steroid receptors in pathobiology of hepatocellular carcinoma.World journal of gastroenterology · 2008Review
- The retrovirus-mediated antisense human telomerase RNA (hTR) gene limits the growth of hepatocellular carcinoma growth in cell culture and animals.Digestive diseases and sciences · 2008Article
- Protection from acute cellular injury using Sleeping Beauty mediated telomerase gene transfer.Biochemical and biophysical research communications · 2007Article
- Increased hepatic telomerase activity in a rat model of iron overload: a role for altered thiol redox state?Free radical biology & medicine · 2007Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimSignificant 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 (hTERT) gene as a form of telomerase therapy in chronic liver disease.
methodsWe examined expression of hTERT 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 17beta-oestradiol. The effects of exogenous oestradiol administration were examined in a carbon tetrachloride (CCl(4)) induced model of liver fibrosis in rats.
resultsExpression of hTERT 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 beta-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 CCl(4) 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.
conclusionThese results suggest that oestradiol acts as a positive modulator of the hTERT gene in the liver. Oestrogen dependent transactivation of the hTERT gene is a new strategy for slowing the progression of chronic liver disease.
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