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Article: Activation of tubular epithelial cells by mesangial-derived TNF-α: Glomerulotubular communication in IgA nephropathy

TitleActivation of tubular epithelial cells by mesangial-derived TNF-α: Glomerulotubular communication in IgA nephropathy
Authors
KeywordsIgA
IgA nephropathy
Macrophage migration inhibitory factor
Mesangial cell
Proximal tubular epithelial cells
Tubulointerstitial injury
Tumor necrosis factor-α
Issue Date2005
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ki/index.html
Citation
Kidney International, 2005, v. 67 n. 2, p. 602-612 How to Cite?
AbstractBackground. IgA nephropathy (IgAN), characterized by mesangial IgA deposition, runs a variable clinical course with tubulointerstitial damage and renal failure in no less than 30% of patients. Histologically, IgA is rarely detected in renal tubules. The direct toxicity by IgA on renal tubules remains uncertain. We hypothesize that mediators released from human mesangial cells (HMC) triggered by IgA deposition may lead to activation of proximal tubular epithelial cells (PTEC). Methods. The binding of IgA to PTEC or HMC was assessed by flow cytometry. IgA-HMC medium was prepared by collecting the spent medium in which growth arrested HMC were incubated with IgA isolated from patients with IgAN, healthy control subjects, or other nephritic control patients. PTEC was cultured with the IgA-HMC medium in the presence or absence of neutralizing antibodies to TNF-α, IL-1β, TGF-β, or PDGF. Gene expression and protein synthesis of TNF-β, MIF, or ICAM-1 by PTEC were determined by RT-PCR and ELISA, respectively. Results. The binding of IgA isolated from patients with IgAN to PTEC was increased when compared to binding of IgA from healthy control subjects (P < 0.005). However, the binding to PTEC was less than one tenth that of HMC in IgAN. The binding to PTEC was not mediated through known IgA receptors, as shown by competitive binding assays and gene expression of the receptors. Despite the in vitro binding, PTEC cultured with isolated IgA exhibited no increased cell proliferation or enhanced synthesis of TNF-α, MIF, or sICAM-1. However, when PTEC were cultured with IgA-HMC medium prepared from IgAN patients, there was enhanced proliferation of PTEC (P < 0.001) and increased synthesis of TNF-α, MIF, and sICAM-1 when compared with PTEC cultured with IgA-HMC medium from control subjects (P < 0.001). The synthesis of MIF and sICAM-1 by PTEC cultured with IgA-HMC medium was reduced by neutralizing antibodies to TNF-α (P < 0.001) but not by neutralizing antibodies to IL-1β, TGF-α, or PDGF. Conclusion. Our finding implicates that TNF-α released from the mesangium after IgA deposition activates renal tubular cells. The glomerulotubular communication could play an important role in the pathogenesis of tubulointerstitial damage in IgAN.
Persistent Identifierhttp://hdl.handle.net/10722/162779
ISSN
2015 Impact Factor: 7.683
2015 SCImago Journal Rankings: 3.181
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, LYYen_US
dc.contributor.authorLeung, JCKen_US
dc.contributor.authorTsang, AWLen_US
dc.contributor.authorTang, SCWen_US
dc.contributor.authorLai, KNen_US
dc.date.accessioned2012-09-05T05:23:27Z-
dc.date.available2012-09-05T05:23:27Z-
dc.date.issued2005en_US
dc.identifier.citationKidney International, 2005, v. 67 n. 2, p. 602-612en_US
dc.identifier.issn0085-2538en_US
dc.identifier.urihttp://hdl.handle.net/10722/162779-
dc.description.abstractBackground. IgA nephropathy (IgAN), characterized by mesangial IgA deposition, runs a variable clinical course with tubulointerstitial damage and renal failure in no less than 30% of patients. Histologically, IgA is rarely detected in renal tubules. The direct toxicity by IgA on renal tubules remains uncertain. We hypothesize that mediators released from human mesangial cells (HMC) triggered by IgA deposition may lead to activation of proximal tubular epithelial cells (PTEC). Methods. The binding of IgA to PTEC or HMC was assessed by flow cytometry. IgA-HMC medium was prepared by collecting the spent medium in which growth arrested HMC were incubated with IgA isolated from patients with IgAN, healthy control subjects, or other nephritic control patients. PTEC was cultured with the IgA-HMC medium in the presence or absence of neutralizing antibodies to TNF-α, IL-1β, TGF-β, or PDGF. Gene expression and protein synthesis of TNF-β, MIF, or ICAM-1 by PTEC were determined by RT-PCR and ELISA, respectively. Results. The binding of IgA isolated from patients with IgAN to PTEC was increased when compared to binding of IgA from healthy control subjects (P < 0.005). However, the binding to PTEC was less than one tenth that of HMC in IgAN. The binding to PTEC was not mediated through known IgA receptors, as shown by competitive binding assays and gene expression of the receptors. Despite the in vitro binding, PTEC cultured with isolated IgA exhibited no increased cell proliferation or enhanced synthesis of TNF-α, MIF, or sICAM-1. However, when PTEC were cultured with IgA-HMC medium prepared from IgAN patients, there was enhanced proliferation of PTEC (P < 0.001) and increased synthesis of TNF-α, MIF, and sICAM-1 when compared with PTEC cultured with IgA-HMC medium from control subjects (P < 0.001). The synthesis of MIF and sICAM-1 by PTEC cultured with IgA-HMC medium was reduced by neutralizing antibodies to TNF-α (P < 0.001) but not by neutralizing antibodies to IL-1β, TGF-α, or PDGF. Conclusion. Our finding implicates that TNF-α released from the mesangium after IgA deposition activates renal tubular cells. The glomerulotubular communication could play an important role in the pathogenesis of tubulointerstitial damage in IgAN.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ki/index.htmlen_US
dc.relation.ispartofKidney Internationalen_US
dc.subjectIgA-
dc.subjectIgA nephropathy-
dc.subjectMacrophage migration inhibitory factor-
dc.subjectMesangial cell-
dc.subjectProximal tubular epithelial cells-
dc.subjectTubulointerstitial injury-
dc.subjectTumor necrosis factor-α-
dc.subject.meshCell Proliferationen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshEpithelial Cells - Pathologyen_US
dc.subject.meshFemaleen_US
dc.subject.meshGlomerular Mesangium - Physiologyen_US
dc.subject.meshGlomerulonephritis, Iga - Pathologyen_US
dc.subject.meshHumansen_US
dc.subject.meshImmunoglobulin A - Metabolismen_US
dc.subject.meshIntercellular Adhesion Molecule-1 - Physiologyen_US
dc.subject.meshKidney Tubules, Proximal - Pathologyen_US
dc.subject.meshMacrophage Migration-Inhibitory Factors - Physiologyen_US
dc.subject.meshMaleen_US
dc.subject.meshReceptors, Fc - Analysisen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Physiologyen_US
dc.titleActivation of tubular epithelial cells by mesangial-derived TNF-α: Glomerulotubular communication in IgA nephropathyen_US
dc.typeArticleen_US
dc.identifier.emailLeung, JCK:jckleung@hku.hken_US
dc.identifier.emailTang, SCW:scwtang@hku.hken_US
dc.identifier.emailLai, KN:knlai@hku.hken_US
dc.identifier.authorityLeung, JCK=rp00448en_US
dc.identifier.authorityTang, SCW=rp00480en_US
dc.identifier.authorityLai, KN=rp00324en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1523-1755.2005.67116.xen_US
dc.identifier.pmid15673307-
dc.identifier.scopuseid_2-s2.0-12344335072en_US
dc.identifier.hkuros99486-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-12344335072&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume67en_US
dc.identifier.issue2en_US
dc.identifier.spage602en_US
dc.identifier.epage612en_US
dc.identifier.isiWOS:000226420600021-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridChan, LYY=35336076700en_US
dc.identifier.scopusauthoridLeung, JCK=7202180349en_US
dc.identifier.scopusauthoridTsang, AWL=7006979244en_US
dc.identifier.scopusauthoridTang, SCW=7403437082en_US
dc.identifier.scopusauthoridLai, KN=7402135706en_US
dc.identifier.citeulike72474-

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