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Article: Transferrin up-regulates chemokine synthesis by human proximal tubular epithelial cells: Implication on mechanism of tubuloglomerular communication in glomerulopathic proteinura

TitleTransferrin up-regulates chemokine synthesis by human proximal tubular epithelial cells: Implication on mechanism of tubuloglomerular communication in glomerulopathic proteinura
Authors
KeywordsChemokine
Glomerular mesangial cell
Interstitial fibrosis
Proteinuria
Tubuloglomerular cross talk
Issue Date2002
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ki/index.html
Citation
Kidney International, 2002, v. 61 n. 5, p. 1655-1665 How to Cite?
AbstractBackground. The pathogenesis of glomerulosclerosis and tubulointerstitial fibrosis in proteinuric renal disease is obscure. We recently showed that transferrin, a key proteinuric component, mediates proximal tubular epithelial cell (PTEC) C3 synthesis. To further examine whether proteinuric tubular injury may induce glomerular inflammation and to characterize the role of transferrin in activating PTEC, glomerular mesangial cells (MC) were exposed to transferrin-activated PTEC culture supernatant and their proliferative and profibrotic responses analyzed. Methods. Human PTEC and MC were obtained by primary culture. Confluent, transferrin-stimulated PTEC were grown in serum-free medium to produce a "conditioned" medium that was incubated with quiescent MC. The proliferative response of MC was then assessed by thymidine uptake, and the expression of fibrogenic factors measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The chemokine profile in PTEC after transferrin treatment was examined by RT-PCR and ELISA. Results. "Conditioned" supernatant from PTEC, which contained the highest amounts of platelet-derived growth factor (PDGF), stimulated MC proliferation compared with serum-free (P = 0.03) or transferrin-containing (P = 0.009) control media. This proliferative response was partially abrogated by treating MC with anti-PDGF. MC expression of PDGF, but not transforming growth factor-β or intercellular cell adhesion molecule-1, was up-regulated by conditioned PTEC medium. Transferrin up-regulated monocyte chemoattractant peptide-1, interleukin-8, and macrophage migration inhibitory factor expression in a time- and dose-dependent fashion, but had no effect on RANTES expression by PTEC. Conclusions. These results provide experimental evidence suggesting that there is a tubuloglomerular "cross-talk" mechanism in the proteinuric state. PTEC-secreted PDGF, which further induces mesangial PDGF, could partially account for the mesangial proliferation frequently observed in proteinuric renal disease. Transferrin is one of the culprit nephrotic proteins leading to tubular overexpression of various proinflammatory chemokines, which may explain the interstitial changes observed in proteinuric states.
Persistent Identifierhttp://hdl.handle.net/10722/162596
ISSN
2015 Impact Factor: 7.683
2015 SCImago Journal Rankings: 3.181
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTang, Sen_HK
dc.contributor.authorLeung, JCKen_HK
dc.contributor.authorTsang, AWLen_HK
dc.contributor.authorHui, YLen_HK
dc.contributor.authorTak, MCen_HK
dc.contributor.authorKar, NLen_HK
dc.date.accessioned2012-09-05T05:21:32Z-
dc.date.available2012-09-05T05:21:32Z-
dc.date.issued2002en_HK
dc.identifier.citationKidney International, 2002, v. 61 n. 5, p. 1655-1665en_HK
dc.identifier.issn0085-2538en_HK
dc.identifier.urihttp://hdl.handle.net/10722/162596-
dc.description.abstractBackground. The pathogenesis of glomerulosclerosis and tubulointerstitial fibrosis in proteinuric renal disease is obscure. We recently showed that transferrin, a key proteinuric component, mediates proximal tubular epithelial cell (PTEC) C3 synthesis. To further examine whether proteinuric tubular injury may induce glomerular inflammation and to characterize the role of transferrin in activating PTEC, glomerular mesangial cells (MC) were exposed to transferrin-activated PTEC culture supernatant and their proliferative and profibrotic responses analyzed. Methods. Human PTEC and MC were obtained by primary culture. Confluent, transferrin-stimulated PTEC were grown in serum-free medium to produce a "conditioned" medium that was incubated with quiescent MC. The proliferative response of MC was then assessed by thymidine uptake, and the expression of fibrogenic factors measured by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The chemokine profile in PTEC after transferrin treatment was examined by RT-PCR and ELISA. Results. "Conditioned" supernatant from PTEC, which contained the highest amounts of platelet-derived growth factor (PDGF), stimulated MC proliferation compared with serum-free (P = 0.03) or transferrin-containing (P = 0.009) control media. This proliferative response was partially abrogated by treating MC with anti-PDGF. MC expression of PDGF, but not transforming growth factor-β or intercellular cell adhesion molecule-1, was up-regulated by conditioned PTEC medium. Transferrin up-regulated monocyte chemoattractant peptide-1, interleukin-8, and macrophage migration inhibitory factor expression in a time- and dose-dependent fashion, but had no effect on RANTES expression by PTEC. Conclusions. These results provide experimental evidence suggesting that there is a tubuloglomerular "cross-talk" mechanism in the proteinuric state. PTEC-secreted PDGF, which further induces mesangial PDGF, could partially account for the mesangial proliferation frequently observed in proteinuric renal disease. Transferrin is one of the culprit nephrotic proteins leading to tubular overexpression of various proinflammatory chemokines, which may explain the interstitial changes observed in proteinuric states.en_HK
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ki/index.htmlen_HK
dc.relation.ispartofKidney Internationalen_HK
dc.subjectChemokineen_HK
dc.subjectGlomerular mesangial cellen_HK
dc.subjectInterstitial fibrosisen_HK
dc.subjectProteinuriaen_HK
dc.subjectTubuloglomerular cross talken_HK
dc.subject.meshAntibodies - Pharmacologyen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshChemokines - Geneticsen_US
dc.subject.meshCulture Media, Conditioned - Pharmacologyen_US
dc.subject.meshEpithelial Cells - Immunology - Metabolismen_US
dc.subject.meshGene Expression Regulation - Immunologyen_US
dc.subject.meshGlomerular Mesangium - Cytology - Immunology - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshKidney Tubules, Proximal - Cytology - Immunology - Metabolismen_US
dc.subject.meshNephritis, Interstitial - Immunology - Physiopathologyen_US
dc.subject.meshPlatelet-Derived Growth Factor - Immunology - Secretionen_US
dc.subject.meshProteinuria - Immunology - Metabolismen_US
dc.subject.meshTransferrin - Pharmacologyen_US
dc.subject.meshUp-Regulation - Drug Effects - Immunologyen_US
dc.titleTransferrin up-regulates chemokine synthesis by human proximal tubular epithelial cells: Implication on mechanism of tubuloglomerular communication in glomerulopathic proteinuraen_HK
dc.typeArticleen_HK
dc.identifier.emailTang, S: scwtang@hku.hken_HK
dc.identifier.emailLeung, JCK: jckleung@hku.hken_HK
dc.identifier.emailTak, MC: dtmchan@hku.hken_HK
dc.identifier.emailKar, NL: knlai@hku.hken_HK
dc.identifier.authorityTang, S=rp00480en_HK
dc.identifier.authorityLeung, JCK=rp00448en_HK
dc.identifier.authorityTak, MC=rp00394en_HK
dc.identifier.authorityKar, NL=rp00324en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1046/j.1523-1755.2002.00301.xen_HK
dc.identifier.pmid11967015-
dc.identifier.scopuseid_2-s2.0-0036233038en_HK
dc.identifier.hkuros67214-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0036233038&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume61en_HK
dc.identifier.issue5en_HK
dc.identifier.spage1655en_HK
dc.identifier.epage1665en_HK
dc.identifier.isiWOS:000175054200010-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridTang, S=7403437082en_HK
dc.identifier.scopusauthoridLeung, JCK=7202180349en_HK
dc.identifier.scopusauthoridTsang, AWL=7006979244en_HK
dc.identifier.scopusauthoridHui, YL=7103107517en_HK
dc.identifier.scopusauthoridTak, MC=7402687700en_HK
dc.identifier.scopusauthoridKar, NL=7402135706en_HK

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