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Article: Podocyte injury induced by mesangial-derived cytokines in IgA nephropathy

TitlePodocyte injury induced by mesangial-derived cytokines in IgA nephropathy
Authors
KeywordsIgA nephropathy
Podocytes
Slit diaphragm
Transforming growth factor-β
Tumour necrosis factor-α
Issue Date2009
PublisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/
Citation
Nephrology Dialysis Transplantation, 2009, v. 24 n. 1, p. 62-72 How to Cite?
AbstractBackground. We have previously documented that human mesangial cell (HMC)-derived tumour necrosis factor-α (TNF-α) is an important mediator involved in the glomerulo-tubular communication in the development of interstitial damage in IgA nephropathy (IgAN). With the strategic position of podocytes, we further examined the function of podocytes in IgAN. Methods. Podocyte markers were examined in renal tissues by immunofluorescence. In vitro experiments were conducted with podocytes cultured with polymeric IgA (pIgA) or conditioned medium prepared from HMC incubated with pIgA (IgA-HMC conditioned medium). Results. Glomerular immunostaining for nephrin or ezrin was significantly weaker in patients with IgAN. The immunostaining of IgA and nephrin was distinctly separate with no co-localization. In vitro experiments revealed no effect of pIgA on the expression of these podocyte proteins as IgA from IgAN patients did not bind to podocytes. In contrast, IgA conditioned medium prepared from IgAN patients down-regulated the expression of these podocyte proteins as well as other podocyte markers (podocin and synaptopodin) in cultured podocytes. The mRNA expression of nephrin, erzin, podocin but not synaptopodin correlated with the degree of proteinuria and creatinine clearance. The down-regulation was reproducible in podocytes cultured with TNF-α or transforming growth factor-β (TGF-β) at concentration comparable to that in the IgA-HMC conditioned medium. The expression of these podocyte proteins was restored partially with a neutralizing antibody against TNF-α or TGF-β and fully with combination of both antibodies. Conclusion. Our finding suggests podocyte markers are reduced in IgAN. An in vitro study implicates that humoral factors (predominantly TNF-α and TGF-β) released from mesangial cells are likely to alter the glomerular permeability in the event of proteinuria and tubulointerstitial injury in IgAN. © The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/59355
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 1.780
ISI Accession Number ID
Funding AgencyGrant Number
L & T Charitable Foundation
House of INDOCAFE
Committee (Hong Kong)HKU 7678/07M
Funding Information:

Dr Chan was partly supported by L & T Charitable Foundation and the House of INDOCAFE. The study was supported by the Research Grant Committee (Hong Kong) (HKU 7678/07M).

References

 

DC FieldValueLanguage
dc.contributor.authorLai, KNen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorChan, LYYen_HK
dc.contributor.authorSaleem, MAen_HK
dc.contributor.authorMathieson, PWen_HK
dc.contributor.authorTam, KYen_HK
dc.contributor.authorXiao, Jen_HK
dc.contributor.authorLai, FMen_HK
dc.contributor.authorTang, SCWen_HK
dc.date.accessioned2010-05-31T03:48:19Z-
dc.date.available2010-05-31T03:48:19Z-
dc.date.issued2009en_HK
dc.identifier.citationNephrology Dialysis Transplantation, 2009, v. 24 n. 1, p. 62-72en_HK
dc.identifier.issn0931-0509en_HK
dc.identifier.urihttp://hdl.handle.net/10722/59355-
dc.description.abstractBackground. We have previously documented that human mesangial cell (HMC)-derived tumour necrosis factor-α (TNF-α) is an important mediator involved in the glomerulo-tubular communication in the development of interstitial damage in IgA nephropathy (IgAN). With the strategic position of podocytes, we further examined the function of podocytes in IgAN. Methods. Podocyte markers were examined in renal tissues by immunofluorescence. In vitro experiments were conducted with podocytes cultured with polymeric IgA (pIgA) or conditioned medium prepared from HMC incubated with pIgA (IgA-HMC conditioned medium). Results. Glomerular immunostaining for nephrin or ezrin was significantly weaker in patients with IgAN. The immunostaining of IgA and nephrin was distinctly separate with no co-localization. In vitro experiments revealed no effect of pIgA on the expression of these podocyte proteins as IgA from IgAN patients did not bind to podocytes. In contrast, IgA conditioned medium prepared from IgAN patients down-regulated the expression of these podocyte proteins as well as other podocyte markers (podocin and synaptopodin) in cultured podocytes. The mRNA expression of nephrin, erzin, podocin but not synaptopodin correlated with the degree of proteinuria and creatinine clearance. The down-regulation was reproducible in podocytes cultured with TNF-α or transforming growth factor-β (TGF-β) at concentration comparable to that in the IgA-HMC conditioned medium. The expression of these podocyte proteins was restored partially with a neutralizing antibody against TNF-α or TGF-β and fully with combination of both antibodies. Conclusion. Our finding suggests podocyte markers are reduced in IgAN. An in vitro study implicates that humoral factors (predominantly TNF-α and TGF-β) released from mesangial cells are likely to alter the glomerular permeability in the event of proteinuria and tubulointerstitial injury in IgAN. © The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/en_HK
dc.relation.ispartofNephrology Dialysis Transplantationen_HK
dc.subjectIgA nephropathyen_HK
dc.subjectPodocytesen_HK
dc.subjectSlit diaphragmen_HK
dc.subjectTransforming growth factor-βen_HK
dc.subjectTumour necrosis factor-αen_HK
dc.subject.meshApoptosisen_HK
dc.subject.meshBase Sequenceen_HK
dc.subject.meshBiological Markers - metabolismen_HK
dc.subject.meshCase-Control Studiesen_HK
dc.subject.meshCell Survivalen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshCulture Media, Conditioneden_HK
dc.subject.meshCytokines - metabolismen_HK
dc.subject.meshCytoskeletal Proteins - geneticsen_HK
dc.subject.meshDNA Primers - geneticsen_HK
dc.subject.meshFemaleen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshGlomerulonephritis, IGA - genetics - immunology - pathologyen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunoglobulin A - metabolismen_HK
dc.subject.meshLymphotoxin-alpha - metabolismen_HK
dc.subject.meshMaleen_HK
dc.subject.meshMembrane Proteins - geneticsen_HK
dc.subject.meshMesangial Cells - immunologyen_HK
dc.subject.meshOsteonectin - geneticsen_HK
dc.subject.meshPodocytes - immunology - metabolism - pathologyen_HK
dc.subject.meshRNA, Messenger - genetics - metabolismen_HK
dc.subject.meshReceptor-Like Protein Tyrosine Phosphatases, Class 3 - geneticsen_HK
dc.subject.meshTumor Necrosis Factor-alpha - metabolismen_HK
dc.titlePodocyte injury induced by mesangial-derived cytokines in IgA nephropathyen_HK
dc.typeArticleen_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailTang, SCW: scwtang@hku.hken_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityTang, SCW=rp00480en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1093/ndt/gfn441en_HK
dc.identifier.pmid18685143en_HK
dc.identifier.scopuseid_2-s2.0-58049206800en_HK
dc.identifier.hkuros149217en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-58049206800&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume24en_HK
dc.identifier.issue1en_HK
dc.identifier.spage62en_HK
dc.identifier.epage72en_HK
dc.identifier.isiWOS:000261908200011-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridChan, LYY=55182644100en_HK
dc.identifier.scopusauthoridSaleem, MA=7103095853en_HK
dc.identifier.scopusauthoridMathieson, PW=7005677484en_HK
dc.identifier.scopusauthoridTam, KY=25930206700en_HK
dc.identifier.scopusauthoridXiao, J=54887023900en_HK
dc.identifier.scopusauthoridLai, FM=7202559720en_HK
dc.identifier.scopusauthoridTang, SCW=7403437082en_HK

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