Show simple item record

dc.contributor.authorHickey, Fionnuala B.
dc.contributor.authorO'Donovan, Helen C.
dc.contributor.authorBrazil, Derek P.
dc.contributor.authorKavanagh, David H.
dc.contributor.authorOliver, Noelynn
dc.contributor.authorMartin, Finian
dc.contributor.authorGodson, Catherine
dc.contributor.authorCrean, John
dc.date.accessioned2014-01-08T12:32:59Z
dc.date.available2014-01-08T12:32:59Z
dc.date.issued2012
dc.date.submitted2012en
dc.identifier.citationO Donovan HC, Hickey FB, Brazil DP, Kavanagh DH, Oliver N, Martin F, Godson C and Crean J, Connective tissue growth factor antagonizes transforming growth factor-?1/Smad signalling in renal mesangial cells, Biochemical Journal, 441, 1, 2012, 499 - 510en
dc.identifier.otherY
dc.identifier.urihttp://hdl.handle.net/2262/67784
dc.descriptionPUBLISHEDen
dc.description.abstractThe critical involvement of TGF-?1 (transforming growth factor-?1) in DN (diabetic nephropathy) is well established. However, the role of CTGF (connective tissue growth factor) in regulating the complex interplay of TGF-?1 signalling networks is poorly understood. The purpose of the present study was to investigate co-operative signalling between CTGF and TGF-?1 and its physiological significance. CTGF was determined to bind directly to the T?RIII (TGF-? type III receptor) and antagonize TGF-?1-induced Smad phosphorylation and transcriptional responses via its N-terminal half. Furthermore, TGF-?1 binding to its receptor was inhibited by CTGF. A consequent shift towards non-canonical TGF-?1 signalling and expression of a unique profile of differentially regulated genes was observed in CTGF/TGF-?1-treated mesangial cells. Decreased levels of Smad2/3 phosphorylation were evident in STZ (streptozotocin)-induced diabetic mice, concomitant with increased levels of CTGF. Knockdown of T?RIII restored TGF-?1-mediated Smad signalling and cell contractility, suggesting that T?RIII is key for CTGFmediated regulation of TGF-?1. Comparison of gene expression profiles from CTGF/TGF-?1-treated mesangial cells and human renal biopsy material with histological diagnosis of DN revealed significant correlation among gene clusters. In summary, mesangial cell responses to TGF-?1 are regulated by cross-talk with CTGF, emphasizing the potential utility of targeting CTGF in DN.en
dc.format.extent499en
dc.format.extent510en
dc.language.isoenen
dc.relation.ispartofseriesBiochemical Journal;
dc.relation.ispartofseries441;
dc.relation.ispartofseries1;
dc.rightsYen
dc.subject.otherdiabetic nephropathy
dc.titleConnective tissue growth factor antagonizes transforming growth factor-?1/Smad signalling in renal mesangial cellsen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/hickeyfb
dc.identifier.rssinternalid88122
dc.rights.ecaccessrightsOpenAccess
dc.identifier.rssurihttp://www.biochemj.org/bj/441/0499/bj4410499.htmen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record