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Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells

Alessio, N
Sandomenico, A
Cipollaro, M
Peluso, G
Galderisi, U
Chambery, A
Published in Cell death and disease. 2013, vol. 4, e911
Abstract Cellular senescence is the permanent arrest of cell cycle, physiologically related to aging and aging-associated diseases. Senescence is also recognized as a mechanism for limiting the regenerative potential of stem cells and to protect cells from cancer development. The senescence program is realized through autocrine/paracrine pathways based on the activation of a peculiar senescence-associated secretory phenotype (SASP). We show here that conditioned media (CM) of senescent mesenchymal stem cells (MSCs) contain a set of secreted factors that are able to induce a full senescence response in young cells. To delineate a hallmark of stem cells SASP, we have characterized the factors secreted by senescent MSC identifying insulin-like growth factor binding proteins 4 and 7 (IGFBP4 and IGFBP7) as key components needed for triggering senescence in young MSC. The pro-senescent effects of IGFBP4 and IGFBP7 are reversed by single or simultaneous immunodepletion of either proteins from senescent-CM. The blocking of IGFBP4/7 also reduces apoptosis and promotes cell growth, suggesting that they may have a pleiotropic effect on MSC biology. Furthermore, the simultaneous addition of rIGFBP4/7 increased senescence and induced apoptosis in young MSC. Collectively, these results suggest the occurrence of novel-secreted factors regulating MSC cellular senescence of potential importance for regenerative medicine and cancer therapy.
Keywords Apoptosis/drug effectsBlotting, WesternCell Aging/drug effects/geneticsCell Differentiation/drug effects/geneticsCell Proliferation/drug effectsCells, CulturedChromatography, LiquidComputational BiologyCulture Media, Conditioned/pharmacologyHumansImmunohistochemistryInsulin-Like Growth Factor Binding Protein 4/genetics/metabolism/pharmacologyInsulin-Like Growth Factor Binding Proteins/genetics/metabolism/pharmacologyTandem Mass Spectrometry
PMID: 24201810
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Article (Published version) (2.8 MB) - public document Free access
Research group Chimie et protéomique clinique (270)
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SEVERINO, Valeria et al. Insulin-like growth factor binding proteins 4 and 7 released by senescent cells promote premature senescence in mesenchymal stem cells. In: Cell death and disease, 2013, vol. 4, p. e911. doi: 10.1038/cddis.2013.445 https://archive-ouverte.unige.ch/unige:41745

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Deposited on : 2014-11-12

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