Characterization of the renal cortical transcriptome following Roux-en-Y gastric bypass surgery in experimental diabetic kidney disease

DC FieldValueLanguage
dc.contributor.authorNair, Meera-
dc.contributor.authorMartin, William P.-
dc.contributor.authorZhernovkov, Vadim-
dc.contributor.authorElliott, Jessie-
dc.contributor.authorFearon, Naomi-
dc.contributor.authorEckhardt, Hans-
dc.contributor.authorMcCormack, Janet-
dc.contributor.authorGodson, Catherine-
dc.contributor.authorBrennan, Eoin-
dc.contributor.authorFandriks, Lars-
dc.contributor.authorDocherty, Neil G.-
dc.contributor.authorle Roux, Carel W.-
dc.date.accessioned2021-11-24T16:11:17Z-
dc.date.available2021-11-24T16:11:17Z-
dc.date.copyright2020 the Authorsen_US
dc.date.issued2020-08-02-
dc.identifier.citationBMJ Open Diabetes Research and Careen_US
dc.identifier.issn2052-4897-
dc.identifier.urihttp://hdl.handle.net/10197/12670-
dc.description.abstractIntroduction Roux-en-Y gastric bypass surgery (RYGB) reduces albuminuria and the long-term incidence of end-stage renal disease in patients with obesity and diabetes. Preclinical modeling in experimental diabetic kidney disease demonstrates that improvements in glomerular structure likely underpin these findings. Research design and methods In adult male Zucker diabetic fatty (ZDF) rats, we profiled the effect of RYGB on weight and metabolic control as well biochemical, structural and ultrastructural indices of diabetic renal injury. Furthermore, we sequenced the renal cortical transcriptome in these rats and used bioinformatic pathway analyses to characterize the transcriptional alterations governing the renal reparative response to RYGB. Results In parallel with improvements in weight and metabolic control, RYGB reduced albuminuria, glomerulomegaly, podocyte stress and podocyte foot process effacement. Pathway analysis of RYGB-induced transcriptomic changes in the renal cortex highlighted correction of disease-associated alterations in fibrosis, inflammation and biological oxidation pathways. RYGB reversed disease-associated changes in the expression of transforming growth factor (TGF)-β superfamily genes that strongly correlated with improvements in structural measures of glomerulopathy. Conclusions Improved glomerular structure in ZDF rats following RYGB is underpinned by pathway level changes, including interruption of the TGF-β-driven early profibrotic programme. Our data provide an important layer of experimental support for clinical evidence demonstrating that RYGB arrests renal damage in patients with obesity and type 2 diabetes.en_US
dc.description.sponsorshipHealth Research Boarden_US
dc.description.sponsorshipHealth Service Executiveen_US
dc.description.sponsorshipScience Foundation Irelanden_US
dc.description.sponsorshipWellcome Trusten_US
dc.format.mediumPrint-
dc.language.isoenen_US
dc.publisherBMJen_US
dc.rightsThis is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.en_US
dc.subjectKidneyen_US
dc.subjectGlomerulusen_US
dc.subjectRNA studiesen_US
dc.subjectZDF rat(s)en_US
dc.subjectBariatric surgeryen_US
dc.subjectMetabolic surgeryen_US
dc.subjectNephropathyen_US
dc.subjectMortalityen_US
dc.subjectExcretionen_US
dc.titleCharacterization of the renal cortical transcriptome following Roux-en-Y gastric bypass surgery in experimental diabetic kidney diseaseen_US
dc.typeJournal Articleen_US
dc.internal.authorcontactotherwilliam.martin@ucd.ieen_US
dc.internal.webversionshttp://dx.doi.org/10.1136/bmjdrc-2019-001113corr1-
dc.statusPeer revieweden_US
dc.identifier.volume8en_US
dc.identifier.issue1en_US
dc.citation.otherArticle Number: e001113en_US
dc.identifier.doi10.1136/bmjdrc-2019-001113-
dc.neeo.contributorNair|Meera|aut|-
dc.neeo.contributorMartin|William P.|aut|-
dc.neeo.contributorZhernovkov|Vadim|aut|-
dc.neeo.contributorElliott|Jessie|aut|-
dc.neeo.contributorFearon|Naomi|aut|-
dc.neeo.contributorEckhardt|Hans|aut|-
dc.neeo.contributorMcCormack|Janet|aut|-
dc.neeo.contributorGodson|Catherine|aut|-
dc.neeo.contributorBrennan|Eoin|aut|-
dc.neeo.contributorFandriks|Lars|aut|-
dc.neeo.contributorDocherty|Neil G.|aut|-
dc.neeo.contributorle Roux|Carel W.|aut|-
dc.description.othersponsorshipSwedish Research Councilen_US
dc.date.updated2020-10-20T19:54:51Z-
dc.identifier.grantid12/YI/B2480-
dc.identifier.grantid15/IA/3152-
dc.identifier.grantid15/US/B3130-
dc.identifier.grantid2015-02733_VR-
dc.identifier.grantidBI 2017_3-
dc.identifier.grantid203930/B/16/Z)-
dc.rights.licensehttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/en_US
item.fulltextWith Fulltext-
item.grantfulltextopen-
Appears in Collections:Conway Institute Research Collection
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