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Article: Transferrin but not albumin mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells

TitleTransferrin but not albumin mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cells
Authors
KeywordsComplement
Proteinuria
Transferrin
Tubulointerstitial disease
Issue Date2001
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/ajkd
Citation
American Journal Of Kidney Diseases, 2001, v. 37 n. 1, p. 94-103 How to Cite?
AbstractComplement is increasingly implicated in the pathogenesis of progressive renal disease resulting from persistent proteinuria. We have previously shown that apical serum proteins stimulate C3 in cultured human proximal tubular epithelial cells (PTECs), and that the stimulant is a nonalbumin compound of 30 to 100 kd. We postulated in this study that transferrin and apotransferrin, also important components of proteinuric urine in this molecularweight range, might be the culprit. Human PTECs were obtained by differential sieving of renal cortical tissue from the normal pole of tumor nephrectomy specimens and characterized to be predominantly of proximal tubular origin. Complement C3 messenger RNA (mRNA) expression was analyzed in confluent growth-arrested PTEC monolayers in media containing different concentrations (2.5 to 20 mg/mL) of transferrin by reverse transcription and polymerase chain reaction. Pure human albumin was used as a control protein. C3 protein secretion was detected and quantified by a sandwich enzyme-linked immunosorbent assay on cell culture supernatants after distinct time points. Transferrin enhanced the rate of C3 secretion in a dose-dependent manner, reaching maximal stimulation at doses of 10 mg/mL. Selected experiments using the Transwell technique showed that C3 release was predominantly apical in the resting state. The addition of 10 mg/mL of transferrin apically but not basolaterally stimulated both apical and basolateral C3 secretion and increased the basolateral-apical ratio of C3 secretion from 0.45 ± 0.16 to 0.93 ± 0.24 (P < 0.02). Constitutive C3 mRNA expression was upregulated by transferrin in a time- and dose-dependent fashion, reaching a peak after 24 hours. A similar degree of C3 upregulation was reproduced when iron-poor transferrin, apotransferrin, was used instead. These results indicate that C3 synthesis in PTECs is upregulated by transferrin, for which protein rather than iron moiety may account for the observed effects. These findings provide evidence linking proteinuria with overexpression of tubular complement. © 2001 by the National Kidney Foundation, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/77077
ISSN
2015 Impact Factor: 6.269
2015 SCImago Journal Rankings: 2.313
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorTang, Sen_HK
dc.contributor.authorLai, KNen_HK
dc.contributor.authorChan, TMen_HK
dc.contributor.authorLan, HYen_HK
dc.contributor.authorHo, SKen_HK
dc.contributor.authorSacks, SHen_HK
dc.date.accessioned2010-09-06T07:28:01Z-
dc.date.available2010-09-06T07:28:01Z-
dc.date.issued2001en_HK
dc.identifier.citationAmerican Journal Of Kidney Diseases, 2001, v. 37 n. 1, p. 94-103en_HK
dc.identifier.issn0272-6386en_HK
dc.identifier.urihttp://hdl.handle.net/10722/77077-
dc.description.abstractComplement is increasingly implicated in the pathogenesis of progressive renal disease resulting from persistent proteinuria. We have previously shown that apical serum proteins stimulate C3 in cultured human proximal tubular epithelial cells (PTECs), and that the stimulant is a nonalbumin compound of 30 to 100 kd. We postulated in this study that transferrin and apotransferrin, also important components of proteinuric urine in this molecularweight range, might be the culprit. Human PTECs were obtained by differential sieving of renal cortical tissue from the normal pole of tumor nephrectomy specimens and characterized to be predominantly of proximal tubular origin. Complement C3 messenger RNA (mRNA) expression was analyzed in confluent growth-arrested PTEC monolayers in media containing different concentrations (2.5 to 20 mg/mL) of transferrin by reverse transcription and polymerase chain reaction. Pure human albumin was used as a control protein. C3 protein secretion was detected and quantified by a sandwich enzyme-linked immunosorbent assay on cell culture supernatants after distinct time points. Transferrin enhanced the rate of C3 secretion in a dose-dependent manner, reaching maximal stimulation at doses of 10 mg/mL. Selected experiments using the Transwell technique showed that C3 release was predominantly apical in the resting state. The addition of 10 mg/mL of transferrin apically but not basolaterally stimulated both apical and basolateral C3 secretion and increased the basolateral-apical ratio of C3 secretion from 0.45 ± 0.16 to 0.93 ± 0.24 (P < 0.02). Constitutive C3 mRNA expression was upregulated by transferrin in a time- and dose-dependent fashion, reaching a peak after 24 hours. A similar degree of C3 upregulation was reproduced when iron-poor transferrin, apotransferrin, was used instead. These results indicate that C3 synthesis in PTECs is upregulated by transferrin, for which protein rather than iron moiety may account for the observed effects. These findings provide evidence linking proteinuria with overexpression of tubular complement. © 2001 by the National Kidney Foundation, Inc.en_HK
dc.languageengen_HK
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/ajkden_HK
dc.relation.ispartofAmerican Journal of Kidney Diseasesen_HK
dc.subjectComplementen_HK
dc.subjectProteinuriaen_HK
dc.subjectTransferrinen_HK
dc.subjectTubulointerstitial diseaseen_HK
dc.subject.meshApoproteins - pharmacologyen_HK
dc.subject.meshCells, Cultureden_HK
dc.subject.meshComplement C3 - biosynthesis - geneticsen_HK
dc.subject.meshDNA, Complementary - analysisen_HK
dc.subject.meshDose-Response Relationship, Drugen_HK
dc.subject.meshGene Expressionen_HK
dc.subject.meshHumansen_HK
dc.subject.meshKidney Tubules, Proximal - metabolismen_HK
dc.subject.meshRNA, Messenger - analysisen_HK
dc.subject.meshTransferrin - metabolism - pharmacologyen_HK
dc.subject.meshUp-Regulationen_HK
dc.subject.meshUrothelium - metabolismen_HK
dc.titleTransferrin but not albumin mediates stimulation of complement C3 biosynthesis in human proximal tubular epithelial cellsen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0272-6386&volume=37&issue=1&spage=94&epage=103&date=2001&atitle=Transferrin+but+not+albumin+mediates+stimulation+of+complement+C3+biosynthesis+in+human+proximal+tubular+epithelial+cellsen_HK
dc.identifier.emailTang, S: scwtang@hku.hken_HK
dc.identifier.emailLai, KN: knlai@hku.hken_HK
dc.identifier.emailChan, TM: dtmchan@hku.hken_HK
dc.identifier.authorityTang, S=rp00480en_HK
dc.identifier.authorityLai, KN=rp00324en_HK
dc.identifier.authorityChan, TM=rp00394en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.pmid11136173-
dc.identifier.scopuseid_2-s2.0-0035162129en_HK
dc.identifier.hkuros61527en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035162129&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume37en_HK
dc.identifier.issue1en_HK
dc.identifier.spage94en_HK
dc.identifier.epage103en_HK
dc.identifier.isiWOS:000166422400013-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridTang, S=7403437082en_HK
dc.identifier.scopusauthoridLai, KN=7402135706en_HK
dc.identifier.scopusauthoridChan, TM=7402687700en_HK
dc.identifier.scopusauthoridLan, HY=7102710832en_HK
dc.identifier.scopusauthoridHo, SK=36839065300en_HK
dc.identifier.scopusauthoridSacks, SH=7103294121en_HK

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