The promoter of human telomerase reverse transcriptase is activated during liver regeneration and hepatocyte proliferation
| Autor: | Lars Zender, Mukesh Kumar, Satyanarayana Ande, Hüseyin Sirma, Julia M. Weise, Britta Witt, Christiane Guguen-Guillouzo, André Lechel, Jitendra K. Meena, Cagatay Günes, Vadim Sakk, Karl-Lenhard Rudolph |
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| Přispěvatelé: | Heinrich-Pette-Institute, Hamburg, Germany., Heinriche-Pette-Institute, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Régulations des équilibres fonctionnels du foie normal et pathologique, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Telomerase Time Factors Cellular differentiation Retinoblastoma Protein Hepatitis MESH: Hepatocytes Mice 0302 clinical medicine E2F2 Transcription Factor E2F7 Transcription Factor Genes Reporter MESH: E2F2 Transcription Factor MESH: Animals Regulatory Elements Transcriptional Promoter Regions Genetic Cells Cultured MESH: E2F7 Transcription Factor MESH: Chromatin Immunoprecipitation 0303 health sciences Liver Disease MESH: Gene Expression Regulation Enzymologic Gastroenterology MESH: Telomerase Cell Differentiation MESH: Lac Operon Telomere MESH: Hepatectomy Liver regeneration medicine.anatomical_structure Lac Operon Liver 030220 oncology & carcinogenesis Hepatocyte MESH: Liver Regeneration RNA Interference MESH: Cells Cultured MESH: Cell Differentiation Transcriptional Activation Chromatin Immunoprecipitation MESH: Mice Transgenic Protein subunit MESH: RNA Interference Mice Transgenic Biology Chromosome Gene Expression Regulation Enzymologic 03 medical and health sciences MESH: Regulatory Elements Transcriptional In vivo MESH: Mice Inbred C57BL MESH: Cell Proliferation MESH: Promoter Regions Genetic medicine Animals Hepatectomy Humans Telomerase reverse transcriptase MESH: Mice 030304 developmental biology Cell Proliferation MESH: Humans Binding Sites Hepatology MESH: Time Factors MESH: Genes Reporter [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology MESH: Retinoblastoma Protein Molecular biology MESH: Male Liver Regeneration Mice Inbred C57BL MESH: Binding Sites Cancer research Hepatocytes MESH: Transcriptional Activation MESH: Liver |
| Zdroj: | Gastroenterology Gastroenterology, 2011, 141 (1), pp.326-37, 337.e1-3. ⟨10.1053/j.gastro.2011.03.047⟩ Gastroenterology, WB Saunders, 2011, 141 (1), pp.326-37, 337.e1-3. ⟨10.1053/j.gastro.2011.03.047⟩ |
| ISSN: | 0016-5085 1528-0012 |
| DOI: | 10.1053/j.gastro.2011.03.047⟩ |
| Popis: | International audience; BACKGROUND & AIMS: Telomerase activity has not been detected in healthy human liver biopsy samples, but it is up-regulated in most human liver tumors. It is not clear whether telomerase is activated in response to acute or chronic liver injury. Telomerase activity is closely associated with expression of its catalytic subunit, telomerase reverse transcriptase (TERT). We analyzed the activity of the human TERT (hTERT) promoter during liver regeneration in vivo and hepatocyte proliferation in vitro. METHODS: We used hTERTp-lacZ transgenic mice, which contain an 8.0-kilobase pair fragment of the hTERT gene promoter, to study the role of TERT in liver regeneration following partial hepatectomy. As an in vitro model, we used the HepaRG cell line as a new model system for human hepatocyte proliferation and differentiation. RESULTS: Activity of the hTERT promoter increased significantly after partial hepatectomy; it was also induced in hepatocytes, based on immunohistologic analysis. Similar to the in vivo results, telomerase activity and hTERT expression were up-regulated in proliferating HepaRG cells and repressed in response to growth arrest and differentiation. Promoter mapping revealed that a proximal 0.3-kilobase pair fragment contains all elements necessary for regulation of hTERT in HepaRG cells. We identified E2F2 and E2F7 as transcription factors that control the differential expression of hTERT in proliferating hepatocytes, in vitro and in vivo. CONCLUSIONS: hTERT is induced in hepatocytes during liver regeneration, indicating a functional role for telomerase in human liver. |
| Databáze: | OpenAIRE |
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