High-mobility group box protein 1: a novel mediator of inflammatory-induced renal epithelial-mesenchymal transition

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dc.contributor.author Lynch, Julie
dc.contributor.author Nolan, Stephen
dc.contributor.author Slattery, Craig
dc.contributor.author Feighery, Ronan
dc.contributor.author Ryan, Michael P.
dc.contributor.author McMorrow, Tara
dc.date.accessioned 2012-06-12T14:17:43Z
dc.date.available 2012-06-12T14:17:43Z
dc.date.copyright 2010 Karger en
dc.date.issued 2010-11-24
dc.identifier.citation American Journal of Nephrology en
dc.identifier.uri http://hdl.handle.net/10197/3631
dc.description.abstract Background: High mobility group box protein 1 (HMGB-1) is a chromatin binding protein that bends DNA thereby facilitating gene transcription. HMGB-1 has also been observed as an extracellular secreted protein in serum of patients with sepsis and has putative intracellular signalling effects regulating the production of interleukin-1 and tumour necrosis factor in a number of inflammatory conditions. Methods: We established a model of immune-mediated epithelial-mesenchymal transition (EMT) in human proximal tubular epithelial cells (PTECs). PTECs were cultured with conditioned medium containing supernatant from activated peripheral blood mononuclear cells (aPBMC). The model was characterised using phenotypic and transcriptomic approaches and suppression subtractive hybridisation was performed to identify differentially regulated genes. Results. Activation of PBMCs resulted in increased secretion of HMGB-1. In addition, treatment of PTECs with aPBMC-conditioned medium resulted in significant upregulation of HMGB-1 in PTECs. Direct treatment of PTECs with recombinant human HMGB-1 induced alterations in epithelial morphology consistent with EMT including reduced E-cadherin expression, increased α-SMA expression and enhanced cell migration. HMGB-1 effects were mediated at least in part by the receptor for advanced glycation end products (RAGE) and through induction of TGF-β1 secretion from PTECs. Conclusions. These results suggest that HMGB-1 is a key mediator of immune-mediated EMT of PTECs and a potentially important signalling molecule in the development of renal fibrosis. en
dc.description.sponsorship Science Foundation Ireland en
dc.description.sponsorship Higher Education Authority en
dc.description.sponsorship Health Research Board en
dc.description.sponsorship Other funder en
dc.format.extent 1094997 bytes
dc.format.mimetype application/pdf
dc.language.iso en en
dc.publisher Karger en
dc.relation.requires Biomolecular and Biomedical Science Research Collection en
dc.subject Renal fibrosis en
dc.subject Epithelial-mesenchymal transition en
dc.subject PBMC en
dc.subject HMGB-1 en
dc.subject.lcsh Kidneys--Fibrosis en
dc.subject.lcsh Chromosomal proteins en
dc.subject.lcsh Blood cells en
dc.subject.lcsh Transforming growth factors-beta en
dc.title High-mobility group box protein 1: a novel mediator of inflammatory-induced renal epithelial-mesenchymal transition en
dc.title.alternative HMGB-1 - a novel mediator of inflammatory-induced renal epithelial mesenchymal transition en
dc.type Journal Article en
dc.internal.availability Full text available en
dc.status Peer reviewed en
dc.identifier.volume 32 en
dc.identifier.issue 6 en
dc.identifier.startpage 590 en
dc.identifier.endpage 602 en
dc.identifier.doi 10.1159/000320485
dc.neeo.contributor Lynch|Julie|aut| en
dc.neeo.contributor Nolan|Stephen|aut| en
dc.neeo.contributor Slattery|Craig|aut| en
dc.neeo.contributor Feighery|Ronan|aut| en
dc.neeo.contributor Ryan|Michael P.|aut| en
dc.neeo.contributor McMorrow|Tara|aut| en
dc.description.othersponsorship Enterprise Ireland en
dc.description.othersponsorship Irish Nephrological Society en
dc.description.othersponsorship Amgen en
dc.description.admin sp, ab, ke, li - TS 15.05.12 en

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