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http://purl.uniprot.org/citations/32304210http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32304210http://www.w3.org/2000/01/rdf-schema#comment"The role of Ras-Mitogen-activated protein kinase (MAPK) signaling in cellular aging is not precisely understood. Recently, we identified Sprouty1 (SPRY1) as a weight-loss target gene in human adipose stem/progenitor cells (ASCs) and showed that Sprouty1 is important for proper regulation of adipogenesis. In the present study, we show that loss-of-function of Sprouty1 by CRISPR/Cas9-mediated genome editing in human ASCs leads to hyper-activation of MAPK signaling and a senescence phenotype. Sprouty1 knockout ASCs undergo an irreversible cell cycle arrest, become enlarged and stain positive for senescence-associated β-galactosidase. Sprouty1 down-regulation leads to DNA double strand breaks, a considerably increased number of senescence-associated heterochromatin foci and induction of p53 and p21Cip1. In addition, we detect an increase of hypo-phosphorylated Retinoblastoma (Rb) protein in SPRY1 knockout ASCs. p16Ink4A is not induced. Moreover, we show that Sprouty1 knockout leads to induction of a senescence-associated secretory phenotype as indicated by the activation of the transcription factors NFκB and C/EBPβ and a significant increase in mRNA expression and secretion of interleukin-8 (IL-8) and CXCL1/GROα. Finally, we demonstrate that adipogenesis is abrogated in senescent SPRY1 knockout ASCs. In conclusion, this study reveals a novel mechanism showing the importance of Sprouty1 for the prevention of senescence and the maintenance of the proliferation and differentiation capacity of human ASCs."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.org/dc/terms/identifier"doi:10.1093/gerona/glaa098"xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Baumgarten S."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Springer J."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Waldegger P."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Wagner S.A."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Mandl M."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Ejaz A."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Brucker C."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Zwerschke W."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Mattesich M."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Pierer G."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Zwierzina M.E."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Hatzmann F.M."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Ritthammer H."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/author"Viertler H.P."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/name"J Gerontol A Biol Sci Med Sci"xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/pages"2308-2319"xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/title"Sprouty1 Prevents Cellular Senescence Maintaining Proliferation and Differentiation Capacity of Human Adipose Stem/Progenitor Cells."xsd:string
http://purl.uniprot.org/citations/32304210http://purl.uniprot.org/core/volume"75"xsd:string
http://purl.uniprot.org/citations/32304210http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32304210
http://purl.uniprot.org/citations/32304210http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/32304210
http://purl.uniprot.org/uniprot/#_O43609-mappedCitation-32304210http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32304210