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dc.contributor.authorIslam, Md Nahidul
dc.contributor.authorGriffin, Tomás P.
dc.contributor.authorSander, Elizabeth
dc.contributor.authorRocks, Stephanie
dc.contributor.authorQazi, Junaid
dc.contributor.authorCabral, Joana
dc.contributor.authorMcCaul, Jasmin
dc.contributor.authorMcMorrow, Tara
dc.contributor.authorGriffin, Matthew D.
dc.date.accessioned2021-01-06T11:38:49Z
dc.date.available2021-01-06T11:38:49Z
dc.date.issued2019-11-19
dc.identifier.citationIslam, Md Nahidul, Griffin, Tomás P., Sander, Elizabeth, Rocks, Stephanie, Qazi, Junaid, Cabral, Joana, McCaul, Jasmin, McMorrow, Tara, Griffin, Matthew D. (2019). Human mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayers. Stem Cell Research & Therapy, 10(1), 329. doi:10.1186/s13287-019-1424-5en_IE
dc.identifier.issn1757-6512
dc.identifier.urihttp://hdl.handle.net/10379/16413
dc.description.abstractBackground: Renal proximal tubular epithelial cells (RPTEC) are dysfunctional in diabetic kidney disease (DKD). Mesenchymal stromal cells (MSC) may modulate DKD pathogenesis through anti-inflammatory mediators. This study aimed to investigate the pro-inflammatory effect of extended exposure to high glucose (HG) concentration on stable RPTEC monolayers and the influence of MSC on this response.Methods: Morphologically stable human RPTEC/TERT1 cell monolayers were exposed to 5 mM and 30 mM (HG) D-glucose or to 5 mM D-glucose + 25 mM D-mannitol (MAN) for 5 days with sequential immunoassays of supernatants and end-point transcriptomic analysis by RNA sequencing. Under the same conditions, MSC-conditioned media (MSC-CM) or MSC-containing transwells were added for days 4-5. Effects of CM from HG- and MAN-exposed RPTEC/MSC co-cultures on cytokine secretion by monocyte-derived macrophages were determined.Results: After 72-80 h, HG resulted in increased RPTEC/TERT1 release of interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1 and neutrophil gelatinase-associated lipocalin (NGAL). The HG pro-inflammatory effect was attenuated by concentrated (10x) MSC-CM and, to a greater extent, by MSC transwell co-culture. Bioinformatics analysis of RNA sequencing data confirmed a predominant effect of HG on inflammation-related mediators and biological processes/KEGG pathways in RPTEC/TERT1 stable monolayers as well as the non-contact-dependent anti-inflammatory effect of MSC. Finally, CM from HG-exposed RPTEC/MSC transwell co-cultures was associated with attenuated secretion of inflammatory mediators by macrophages compared to CM from HG-stimulated RPTEC alone.Conclusions: Stable RPTEC monolayers demonstrate delayed pro-inflammatory response to HG that is attenuated by close proximity to human MSC. In DKD, this MSC effect has potential to modulate hyperglycemia-associated RPTEC/macrophage cross-talk.en_IE
dc.description.sponsorshipThe research was supported by a grant from the European Commission [Horizon 2020 Collaborative Health Project NEPHSTROM (grant number 634086; TPG, MNI, MDG)]. Other funding sources that contributed to the work were grants from the European Commission [FP7 Collaborative Health Project VISICORT (grant number 602470; MDG, JC)], from Science Foundation Ireland [REMEDI Strategic Research Cluster (grant number 09/SRC-B1794; MDG) and CÚRAM Research Centre (grant number 13/RC/2073; MDG)], from the Health Research board of Ireland (grant number HRA_POR/2013/341; JC, MDG) and the European Regional Development Fund. TPG is supported by a Hardiman Scholarship from the College of Medicine, Nursing and Health Science, National University of Ireland Galway and a bursary from the Irish Endocrine Society/Royal College of Physicians of Ireland. JMcC and TMcM are funded by Science Foundation Ireland (grant number 12/IP/1686) and by the School of Biomolecular and Biomedical Science, University College Dublin.en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherBMCen_IE
dc.relation.ispartofStem Cell Research & Therapyen
dc.subjectMONOCYTE CHEMOATTRACTANT PROTEIN-1en_IE
dc.subjectFACTOR-KAPPA-Ben_IE
dc.subjectINDUCED DIABETIC-NEPHROPATHYen_IE
dc.subjectEPITHELIAL-CELLSen_IE
dc.subjectSTEM-CELLSen_IE
dc.subjectTHERAPEUTIC TARGETen_IE
dc.subjectKIDNEYen_IE
dc.subjectINJURYen_IE
dc.subjectACTIVATIONen_IE
dc.subjectEXPRESSIONen_IE
dc.titleHuman mesenchymal stromal cells broadly modulate high glucose-induced inflammatory responses of renal proximal tubular cell monolayersen_IE
dc.typeArticleen_IE
dc.date.updated2020-12-20T09:16:00Z
dc.identifier.doi10.1186/s13287-019-1424-5
dc.local.publishedsourcehttps://doi.org/10.1186/s13287-019-1424-5en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderHorizon 2020en_IE
dc.contributor.funderSeventh Framework Programmeen_IE
dc.contributor.funderScience Foundation Irelanden_IE
dc.contributor.funderHealth Research Boarden_IE
dc.contributor.funderEuropean Regional Development Funden_IE
dc.contributor.funderHardiman Research Scholarship, National University of Ireland Galwayen_IE
dc.contributor.funderIrish Endocrine Society/Royal College of Physicians of Irelanden_IE
dc.internal.rssid19576301
dc.local.contactMatthew Dallas Griffin, Remedi, Biomedical Sciences Buil, Corrib Village, Dangan, Nui Galway. 5436 Email: matthew.griffin@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
dcterms.projectinfo:eu-repo/grantAgreement/EC/H2020::RIA/634086/EU/Novel Stromal Cell Therapy for Diabetic Kidney Disease/NEPHSTROMen_IE
dcterms.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/602470/EU/Adverse Immune Signatures and their Prevention in Corneal Transplantation/VISICORTen_IE
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Strategic Research Cluster/09/SRC/B1794/IE/SRC REMEDI: REMEDI-2: From Research to Human Therapy/en_IE
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/13/RC/2073/IE/C�RAM - Centre for Research in Medical Devices/en_IE
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IP/1686/IE/Molecular mechanisms of cilia loss in mammalian epithelial cells/en_IE
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