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Article: Anti-macrophage migration inhibitory factor reduces transforming growth factor-β1 expression in experimental IgA nephropathy

TitleAnti-macrophage migration inhibitory factor reduces transforming growth factor-β1 expression in experimental IgA nephropathy
Authors
Issue Date2004
PublisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/
Citation
Nephrology Dialysis Transplantation, 2004, v. 19 n. 8, p. 1976-1985 How to Cite?
AbstractBackground. In human glomerulonephritis, including immunoglobulin-A nephropathy (IgAN), glomerular expression of macrophage migration inhibitory factor (MIF) is found to correlate with progressive renal injury. We have shown previously that polymeric IgA is capable of inducing MIF production in cultured human mesangial cells, suggesting a role in inducing inflammatory injury in IgAN. Herein, we examined whether IgA deposition and the subsequent renal injury can be ameliorated with anti-MIF treatment in an experimental murine model of IgAN. Methods. Glomerular IgA deposition was induced in 4-week-old BALB/c mice by intravenous injection of immune complexes consisting of dinitrophenyl-conjugated bovine serum albumin (DNP BSA) and IgA MOPC-315 myeloma anti-DNP antibodies. To determine the therapeutic effect of anti-MIF, mice were given anti-MIF (5 mg/kg) or isotypic control antibody intravenously 2 h before the immune complexes administration. The mice were sacrificed 48 h after injection of DNP-IgA. Proteinuria and haematuria were determined and the kidneys were removed for histopathology, immunostaining and immunoblotting. The effect of exogenous MIF on production of TGF-β1 by cultured mesangial cells was also examined. Results. IgA deposits were detected in glomeruli of all mice receiving the immune complexes while no glomerular deposit was detected in the control mice. Microscopic haematuria and mesangial hypercellularity were present in mice of the three experimental groups and were absent in the control group. Proteinuria was absent in all groups. Anti-MIF treatment also resulted in decreased renal expression of TGF-β1. Moreover, the reduction in TGF-β1 expression was confined mainly to glomerular mesangium. An in vitro culture experiment demonstrated that MIF increased TGF-β1 production in a time- and dose-dependent fashion. MIF-induced TGF-β1 synthesis was abolished by incubating cells with neutralizing antibody against MIF. Conclusions. Our finding shows that anti-MIF treatment can ameliorate kidney injury and reduce glomerular TGF-β1 expression in an experimental model of IgAN. © ERA-EDTA 2004; all rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/163167
ISSN
2015 Impact Factor: 4.085
2015 SCImago Journal Rankings: 1.780
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLeung, JCKen_US
dc.contributor.authorChan, LYYen_US
dc.contributor.authorTsang, AWLen_US
dc.contributor.authorLiu, EWLen_US
dc.contributor.authorLam, MFen_US
dc.contributor.authorTang, SCWen_US
dc.contributor.authorLai, KNen_US
dc.date.accessioned2012-09-05T05:28:22Z-
dc.date.available2012-09-05T05:28:22Z-
dc.date.issued2004en_US
dc.identifier.citationNephrology Dialysis Transplantation, 2004, v. 19 n. 8, p. 1976-1985en_US
dc.identifier.issn0931-0509en_US
dc.identifier.urihttp://hdl.handle.net/10722/163167-
dc.description.abstractBackground. In human glomerulonephritis, including immunoglobulin-A nephropathy (IgAN), glomerular expression of macrophage migration inhibitory factor (MIF) is found to correlate with progressive renal injury. We have shown previously that polymeric IgA is capable of inducing MIF production in cultured human mesangial cells, suggesting a role in inducing inflammatory injury in IgAN. Herein, we examined whether IgA deposition and the subsequent renal injury can be ameliorated with anti-MIF treatment in an experimental murine model of IgAN. Methods. Glomerular IgA deposition was induced in 4-week-old BALB/c mice by intravenous injection of immune complexes consisting of dinitrophenyl-conjugated bovine serum albumin (DNP BSA) and IgA MOPC-315 myeloma anti-DNP antibodies. To determine the therapeutic effect of anti-MIF, mice were given anti-MIF (5 mg/kg) or isotypic control antibody intravenously 2 h before the immune complexes administration. The mice were sacrificed 48 h after injection of DNP-IgA. Proteinuria and haematuria were determined and the kidneys were removed for histopathology, immunostaining and immunoblotting. The effect of exogenous MIF on production of TGF-β1 by cultured mesangial cells was also examined. Results. IgA deposits were detected in glomeruli of all mice receiving the immune complexes while no glomerular deposit was detected in the control mice. Microscopic haematuria and mesangial hypercellularity were present in mice of the three experimental groups and were absent in the control group. Proteinuria was absent in all groups. Anti-MIF treatment also resulted in decreased renal expression of TGF-β1. Moreover, the reduction in TGF-β1 expression was confined mainly to glomerular mesangium. An in vitro culture experiment demonstrated that MIF increased TGF-β1 production in a time- and dose-dependent fashion. MIF-induced TGF-β1 synthesis was abolished by incubating cells with neutralizing antibody against MIF. Conclusions. Our finding shows that anti-MIF treatment can ameliorate kidney injury and reduce glomerular TGF-β1 expression in an experimental model of IgAN. © ERA-EDTA 2004; all rights reserved.en_US
dc.languageengen_US
dc.publisherOxford University Press. The Journal's web site is located at http://ndt.oxfordjournals.org/en_US
dc.relation.ispartofNephrology Dialysis Transplantationen_US
dc.rightsNephrology, Dialysis, Transplantation. Copyright © Oxford University Press.-
dc.subject.meshAnimalsen_US
dc.subject.meshAntibodies, Monoclonalen_US
dc.subject.meshGene Expressionen_US
dc.subject.meshGlomerulonephritis, Iga - Metabolismen_US
dc.subject.meshImmunoblottingen_US
dc.subject.meshImmunohistochemistryen_US
dc.subject.meshMacrophage Migration-Inhibitory Factors - Immunologyen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred Balb Cen_US
dc.subject.meshTransforming Growth Factor Beta - Biosynthesis - Genetics - Metabolismen_US
dc.subject.meshTransforming Growth Factor Beta1en_US
dc.subject.meshUp-Regulation - Physiologyen_US
dc.titleAnti-macrophage migration inhibitory factor reduces transforming growth factor-β1 expression in experimental 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_OA_fulltexten_US
dc.identifier.doi10.1093/ndt/gfh323en_US
dc.identifier.pmid15187193-
dc.identifier.scopuseid_2-s2.0-4344717190en_US
dc.identifier.hkuros99274-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-4344717190&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume19en_US
dc.identifier.issue8en_US
dc.identifier.spage1976en_US
dc.identifier.epage1985en_US
dc.identifier.isiWOS:000223114000006-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLeung, JCK=7202180349en_US
dc.identifier.scopusauthoridChan, LYY=35336076700en_US
dc.identifier.scopusauthoridTsang, AWL=7006979244en_US
dc.identifier.scopusauthoridLiu, EWL=36120756500en_US
dc.identifier.scopusauthoridLam, MF=7202630163en_US
dc.identifier.scopusauthoridTang, SCW=7403437082en_US
dc.identifier.scopusauthoridLai, KN=7402135706en_US

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