Permanent cystathionine-β-Synthase gene knockdown promotes inflammation and oxidative stress in immortalized human adipose-derived mesenchymal stem cells, enhancing their adipogenic capacity
dc.contributor.author
dc.date.accessioned
2021-02-22T09:31:33Z
dc.date.available
2021-02-22T09:31:33Z
dc.date.issued
2020-08-02
dc.identifier.issn
2213-2317
dc.identifier.uri
dc.description.abstract
In the present study, we aimed to investigate the impact of permanent cystathionine-β-Synthase (CBS) gene knockdown in human telomerase reverse transcriptase (hTERT) immortalized human adipose-derived mesenchymal stem cells (ASC52telo) and in their capacity to differentiate into adipocytes. CBS gene KD in ASC52telo cells led to increased cellular inflammation (IL6, CXCL8, TNF) and oxidative stress markers (increased intracellular reactive oxygen species and decreased reduced glutathione levels) in parallel to decreased H2S production and rejuvenation (LC3 and SIRT1)-related gene expression. In addition, CBS gene KD in ASC52telo cells resulted in altered mitochondrial respiratory function, characterised by decreased basal respiration (specifically proton leak) and spare respiratory capacity, without significant effects on cell viability and proliferation. In this context, shCBS-ASC52telo cells displayed enhanced adipogenic (FABP4, ADIPOQ, SLC2A4, CEBPA, PPARG)-, lipogenic (FASN, DGAT1)- and adipocyte (LEP, LBP)-related gene expression markers, decreased expression of proinflammatory cytokines, and increased intracellular lipid accumulation during adipocyte differentiation compared to control ASC52telo cells. Otherwise, the increased adipogenic potential of shCBS-ASC52telo cells was detrimental to the ability to differentiate into osteogenic linage. In conclusion, this study demonstrated that permanent CBS gene KD in ASC52telo cells promotes a cellular senescence phenotype with a very increased adipogenic potential, promoting a non-physiological enhanced adipocyte differentiation with excessive lipid storage
dc.description.sponsorship
This work was partially supported by research grants PI15/01934, PI16/01173 and PI19/01712 from the Instituto de Salud Carlos III from Spain and VII Spanish Diabetes Association grants to Basic Diabetes Research Projects led by young researchers, CIBEROBN Fisiopatología de la Obesidad y Nutrici ́on is an initiative from the Instituto de Salud Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) from Spain. We acknowledge the technical support in L1 synthesis of Xavier Ribas (UdG) and Miquel Costas (UdG)
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.relation.isformatof
Reproducció digital del document publicat a: https://doi.org/10.1016/j.redox.2020.101668
dc.relation.ispartof
Redox Biology, 2020, vol. 42, art.núm. 101668
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Articles publicats (D-CM)
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.uri
dc.title
Permanent cystathionine-β-Synthase gene knockdown promotes inflammation and oxidative stress in immortalized human adipose-derived mesenchymal stem cells, enhancing their adipogenic capacity
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
032946
dc.type.peerreviewed
peer-reviewed