Gene expression profiling of hypoxic response in different models of senescent endothelial cells.
Axitinib
Doxorubicin
Endothelial cells
Hypoxia
RNAseq
SASP
Senescence
Journal
Aging clinical and experimental research
ISSN: 1720-8319
Titre abrégé: Aging Clin Exp Res
Pays: Germany
ID NLM: 101132995
Informations de publication
Date de publication:
Jul 2021
Jul 2021
Historique:
received:
28
06
2019
accepted:
15
10
2019
pubmed:
2
11
2019
medline:
6
7
2021
entrez:
2
11
2019
Statut:
ppublish
Résumé
Endothelial cells senescence is a physiological process affecting vascular integrity. It can contribute to heart and arterial stiffening and remodeling, impaired angiogenesis, defective vascular repair, and with an increasing prevalence of atherosclerosis. Drugs used as antineoplastic therapies, targeting tumor as well as endothelial cells, can also trigger endothelial cells senescence. We demonstrated that a short pulse of axitinib, a specific inhibitor of vascular endothelial growth factor receptors, induces cell senescence of endothelial cells. Here, we performed a high-throughput gene expression analysis to characterize the response of proliferating versus senescent endothelial cells to hypoxia, the main trigger of neo-angiogenetic phenomena in tumors. We compared the response to hypoxia of replicative senescent cells, with that of axitinib or of DNA damage-induced senescence. Overall, we enlightened common and specific responses to different senescence inducers and changes in the Senescent Associated Secretory Phenotype.
Identifiants
pubmed: 31673993
doi: 10.1007/s40520-019-01390-5
pii: 10.1007/s40520-019-01390-5
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1993-2001Références
Erusalimsky JD (2009) Vascular endothelial senescence: from mechanisms to pathophysiology. J Appl Physiol 106:326–332
doi: 10.1152/japplphysiol.91353.2008
Kovacic JC, Moreno P, Nabel EG et al (2011) Cellular senescence, vascular disease, and aging. Circulation 123:1900–1910
doi: 10.1161/CIRCULATIONAHA.110.009118
Demaria M, O’Leary MN, Chang J et al (2017) Cellular senescence promotes adverse effects of chemotherapy and cancer relapse. Cancer Discov 7:165–176
doi: 10.1158/2159-8290.CD-16-0241
Mongiardi MP, Radice G, Piras M et al (2019) Axitinib exposure triggers endothelial cells senescence through ROS accumulation and ATM activation. Oncogene 1:1. https://doi.org/10.1038/s41388-019-0798-2
doi: 10.1038/s41388-019-0798-2
Bencokova Z, Kaufmann MR, Pires IM et al (2009) ATM activation and signaling under hypoxic conditions. Mol Cell Biol 29:526–537
doi: 10.1128/MCB.01301-08
Di Mitri D, Alimonti A (2016) Non-cell-autonomous regulation of cellular senescence in cancer. Trends Cell Biol 26:215–226
doi: 10.1016/j.tcb.2015.10.005
Coppé J-P, Patil CK, Rodier F et al (2008) Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 6:e301
doi: 10.1371/journal.pbio.0060301
Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114–2120
doi: 10.1093/bioinformatics/btu170
Langmead B, Trapnell C, Salzberg S (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10:R25
doi: 10.1186/gb-2009-10-3-r25
Trapnell C, Pachter L, Salzberg SL (2009) TopHat: discovering splice junctions withRNA-Seq. Bioinformatics 25:1105–1111
doi: 10.1093/bioinformatics/btp120
Trapnell C, Roberts A, Goff L et al (2013) Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat Protoc 7:562–578
doi: 10.1038/nprot.2012.016