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Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts
Cellular senescence can be induced by a variety of mechanisms, and recent data suggest a key role for cytokine networks to maintain the senescent state. Here, we have used a proteomic LC-MS/MS approach to identify new extracellular regulators of senescence in human fibroblasts. We identified 26 extr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Science Ireland
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192261/ https://www.ncbi.nlm.nih.gov/pubmed/21820463 http://dx.doi.org/10.1016/j.mad.2011.07.005 |
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author | Micutkova, Lucia Diener, Thomas Li, Chen Rogowska-Wrzesinska, Adelina Mueck, Christoph Huetter, Eveline Weinberger, Birgit Grubeck-Loebenstein, Beatrix Roepstorff, Peter Zeng, Rong Jansen-Duerr, Pidder |
author_facet | Micutkova, Lucia Diener, Thomas Li, Chen Rogowska-Wrzesinska, Adelina Mueck, Christoph Huetter, Eveline Weinberger, Birgit Grubeck-Loebenstein, Beatrix Roepstorff, Peter Zeng, Rong Jansen-Duerr, Pidder |
author_sort | Micutkova, Lucia |
collection | PubMed |
description | Cellular senescence can be induced by a variety of mechanisms, and recent data suggest a key role for cytokine networks to maintain the senescent state. Here, we have used a proteomic LC-MS/MS approach to identify new extracellular regulators of senescence in human fibroblasts. We identified 26 extracellular proteins with significantly different abundance in conditioned media from young and senescent fibroblasts. Among these was insulin-like growth factor binding protein-6 (IGFBP-6), which was chosen for further analysis. When IGFBP-6 gene expression was downregulated, cell proliferation was inhibited and apoptotic cell death was increased. Furthermore, downregulation of IGFBP-6 led to premature entry into cellular senescence. Since IGFBP-6 overexpression increased cellular lifespan, the data suggest that IGFBP-6, in contrast to other IGF binding proteins, is a negative regulator of cellular senescence in human fibroblasts. |
format | Online Article Text |
id | pubmed-3192261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Elsevier Science Ireland |
record_format | MEDLINE/PubMed |
spelling | pubmed-31922612011-10-31 Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts Micutkova, Lucia Diener, Thomas Li, Chen Rogowska-Wrzesinska, Adelina Mueck, Christoph Huetter, Eveline Weinberger, Birgit Grubeck-Loebenstein, Beatrix Roepstorff, Peter Zeng, Rong Jansen-Duerr, Pidder Mech Ageing Dev Article Cellular senescence can be induced by a variety of mechanisms, and recent data suggest a key role for cytokine networks to maintain the senescent state. Here, we have used a proteomic LC-MS/MS approach to identify new extracellular regulators of senescence in human fibroblasts. We identified 26 extracellular proteins with significantly different abundance in conditioned media from young and senescent fibroblasts. Among these was insulin-like growth factor binding protein-6 (IGFBP-6), which was chosen for further analysis. When IGFBP-6 gene expression was downregulated, cell proliferation was inhibited and apoptotic cell death was increased. Furthermore, downregulation of IGFBP-6 led to premature entry into cellular senescence. Since IGFBP-6 overexpression increased cellular lifespan, the data suggest that IGFBP-6, in contrast to other IGF binding proteins, is a negative regulator of cellular senescence in human fibroblasts. Elsevier Science Ireland 2011-10 /pmc/articles/PMC3192261/ /pubmed/21820463 http://dx.doi.org/10.1016/j.mad.2011.07.005 Text en © 2011 Elsevier Ireland Ltd. https://creativecommons.org/licenses/by-nc-nd/3.0/ Open Access under CC BY-NC-ND 3.0 (https://creativecommons.org/licenses/by-nc-nd/3.0/) license |
spellingShingle | Article Micutkova, Lucia Diener, Thomas Li, Chen Rogowska-Wrzesinska, Adelina Mueck, Christoph Huetter, Eveline Weinberger, Birgit Grubeck-Loebenstein, Beatrix Roepstorff, Peter Zeng, Rong Jansen-Duerr, Pidder Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts |
title | Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts |
title_full | Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts |
title_fullStr | Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts |
title_full_unstemmed | Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts |
title_short | Insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts |
title_sort | insulin-like growth factor binding protein-6 delays replicative senescence of human fibroblasts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192261/ https://www.ncbi.nlm.nih.gov/pubmed/21820463 http://dx.doi.org/10.1016/j.mad.2011.07.005 |
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