| hTERT alone immortalizes epithelial cells of renal proximal tubules without changing their functional characteristics. | |
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MedLine Citation:
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PMID: 18715936 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Telomere-dependent replicative senescence is one of the mechanisms that limit the number of population doublings of normal human cells. By overexpression of telomerase, cells of various origins have been successfully immortalized without changing the phenotype. While a limited number of telomerase-immortalized cells of epithelial origin are available, none of renal origin has been reported so far. Here we have established simple and safe conditions that allow serial passaging of renal proximal tubule epithelial cells (RPTECs) until entry into telomere-dependent replicative senescence. As reported for other cells, senescence of RPTECs is characterized by arrest in G1 phase, shortened telomeres, staining for senescence-associated beta-galactosidase, and accumulation of gamma-H2AX foci. Furthermore, ectopic expression of the catalytic subunit of telomerase (TERT) was sufficient to immortalize these cells. Characterization of immortalized RPTEC/TERT1 cells shows characteristic morphological and functional properties like formation of tight junctions and domes, expression of aminopeptidase N, cAMP induction by parathyroid hormone, sodium-dependent phosphate uptake, and the megalin/cubilin transport system. No genomic instability within up to 90 population doublings has been observed. Therefore, these cells are proposed as a valuable model system not only for cell biology but also for toxicology, drug screening, biogerontology, as well as tissue engineering approaches. |
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Authors:
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Matthias Wieser; Guido Stadler; Paul Jennings; Berthold Streubel; Walter Pfaller; Peter Ambros; Claus Riedl; Hermann Katinger; Johannes Grillari; Regina Grillari-Voglauer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-08-20 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 295 ISSN: 1931-857X ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2008 Nov |
Date Detail:
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Created Date: 2008-11-06 Completed Date: 2009-02-09 Revised Date: 2011-04-28 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F1365-75 Citation Subset: IM |
Affiliation:
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Aging and Immortalization Research, Institute of Applied Microbiology, Department of Biotechnology, BOKU-University of Natural Resources and Applied Sciences, Vienna, Austria. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antigens, CD13
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metabolism Cadherins / metabolism Cell Aging / physiology Cell Cycle / physiology Cell Line, Transformed Cell Proliferation* Cilia / ultrastructure Cyclic AMP / metabolism Epithelial Cells / cytology, metabolism*, physiology Histones / metabolism Humans Hydrogen-Ion Concentration Kidney Tubules, Proximal / cytology Membrane Proteins / metabolism Microscopy, Electron Microvilli / ultrastructure Parathyroid Hormone / pharmacology Receptors, Cell Surface / genetics, metabolism Sodium-Phosphate Cotransporter Proteins / metabolism Telomerase / genetics*, metabolism Tight Junctions / metabolism, ultrastructure Transfection beta-Galactosidase / metabolism gamma-Glutamyltransferase / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Cadherins; 0/H2AFX protein, human; 0/Histones; 0/Membrane Proteins; 0/Parathyroid Hormone; 0/Receptors, Cell Surface; 0/Sodium-Phosphate Cotransporter Proteins; 0/occludin; 60-92-4/Cyclic AMP; EC 2.3.2.2/gamma-Glutamyltransferase; EC 2.7.7.49/Telomerase; EC 3.2.1.23/beta-Galactosidase; EC 3.4.11.2/Antigens, CD13 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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