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Conference Paper: Hyaluronan in the pathogenesis of lupus nephritis in NZB/W mice and the effect of 4-methylumbelliferone

TitleHyaluronan in the pathogenesis of lupus nephritis in NZB/W mice and the effect of 4-methylumbelliferone
Authors
KeywordsMedical sciences
Rheumatology
Issue Date2010
PublisherSage Publications Ltd. The Journal's web site is located at http://lup.sagepub.com
Citation
The 9th International Congress on Systemic Lupus Erythematosus (SLE), Vancouver, Canada, 24-27 June 2010. In Lupus, 2010, v. 19 n. 1, suppl., p. 115-116, abstract no. PO1.M.4 How to Cite?
AbstractOBJECTIVES: Renal inflammation is a hallmark of lupus nephritis. Hyaluronan (HA) is a non-sulfated glycosaminoglycan ubiquitous in the extracellular environment of all cells. Tissue inflammation and fibrosis are associated with increased HA levels. Increased glomerular and tubular-interstitial HA expression has been shown in lupus nephritis, but its role in pathogenesis remains to be defined. Using 4-methylumbelliferone (MU), a specific inhibitor of HA synthesis, we examined the role of HA on renal histopathology and clinical manifestations in NZB/W mice with lupus nephritis. METHODS: Twenty-four female NZB/W mice with active nephritis denoted by persistent proteinuria >300mg/dl were divided into 4 groups and administered saline or MU (0.5, 1.0 or 5.0 mg/kg/day) by oral gavage for 12 weeks. They were then sacrificed and the urine, blood and kidneys analysed. RESULTS: MU significantly reduced serum HA levels in a dose-dependent manner compared to controls (p<0.05). This was associated with reductions in anti-dsDNA antibody titre (1316±718ng/ml vs 807±381ng/ml, control vs 5mg/kg/day MU, p<0.05), urine protein-to-creatinine ratio (23 vs 13 mg/mg creatinine for corresponding groups, p<0.05), and splenomegaly (0.16g vs 0.12 g for corresponding groups, p<0.05). Mice with active nephritis showed glomerular hypertrophy and increased intra-renal expression of CD4, CD8, CD19, CD23, CD45 and Mac-1. The intra-glomerular expression of HA and its receptor CD44, as well as that of IL-6 and MCP-1, was also increased. These changes were abrogated in mice treated with MU at 1 and 5 mg/kg/day. CONCLUSIONS: Our data suggest that HA participates in the pathogenesis of inflammation and histopathologic manifestations of renal injury in lupus nephritis, and thus may be a potential target for therapy.
DescriptionPoster Presentations - PO1M Pathogenesis: PO1.M.4
Persistent Identifierhttp://hdl.handle.net/10722/126366
ISSN
2015 Impact Factor: 2.118
2015 SCImago Journal Rankings: 0.878

 

DC FieldValueLanguage
dc.contributor.authorTse, WWen_HK
dc.contributor.authorYung, Sen_HK
dc.contributor.authorChan, DTMen_HK
dc.date.accessioned2010-10-31T12:24:35Z-
dc.date.available2010-10-31T12:24:35Z-
dc.date.issued2010en_HK
dc.identifier.citationThe 9th International Congress on Systemic Lupus Erythematosus (SLE), Vancouver, Canada, 24-27 June 2010. In Lupus, 2010, v. 19 n. 1, suppl., p. 115-116, abstract no. PO1.M.4en_HK
dc.identifier.issn0961-2033-
dc.identifier.urihttp://hdl.handle.net/10722/126366-
dc.descriptionPoster Presentations - PO1M Pathogenesis: PO1.M.4-
dc.description.abstractOBJECTIVES: Renal inflammation is a hallmark of lupus nephritis. Hyaluronan (HA) is a non-sulfated glycosaminoglycan ubiquitous in the extracellular environment of all cells. Tissue inflammation and fibrosis are associated with increased HA levels. Increased glomerular and tubular-interstitial HA expression has been shown in lupus nephritis, but its role in pathogenesis remains to be defined. Using 4-methylumbelliferone (MU), a specific inhibitor of HA synthesis, we examined the role of HA on renal histopathology and clinical manifestations in NZB/W mice with lupus nephritis. METHODS: Twenty-four female NZB/W mice with active nephritis denoted by persistent proteinuria >300mg/dl were divided into 4 groups and administered saline or MU (0.5, 1.0 or 5.0 mg/kg/day) by oral gavage for 12 weeks. They were then sacrificed and the urine, blood and kidneys analysed. RESULTS: MU significantly reduced serum HA levels in a dose-dependent manner compared to controls (p<0.05). This was associated with reductions in anti-dsDNA antibody titre (1316±718ng/ml vs 807±381ng/ml, control vs 5mg/kg/day MU, p<0.05), urine protein-to-creatinine ratio (23 vs 13 mg/mg creatinine for corresponding groups, p<0.05), and splenomegaly (0.16g vs 0.12 g for corresponding groups, p<0.05). Mice with active nephritis showed glomerular hypertrophy and increased intra-renal expression of CD4, CD8, CD19, CD23, CD45 and Mac-1. The intra-glomerular expression of HA and its receptor CD44, as well as that of IL-6 and MCP-1, was also increased. These changes were abrogated in mice treated with MU at 1 and 5 mg/kg/day. CONCLUSIONS: Our data suggest that HA participates in the pathogenesis of inflammation and histopathologic manifestations of renal injury in lupus nephritis, and thus may be a potential target for therapy.-
dc.languageengen_HK
dc.publisherSage Publications Ltd. The Journal's web site is located at http://lup.sagepub.com-
dc.relation.ispartofLupus-
dc.rightsLupus. Copyright © Sage Publications Ltd.-
dc.subjectMedical sciences-
dc.subjectRheumatology-
dc.titleHyaluronan in the pathogenesis of lupus nephritis in NZB/W mice and the effect of 4-methylumbelliferoneen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0961-2033&volume=19&issue=1, suppl.&spage=115&epage=116&date=2010&atitle=Hyaluronan+in+the+pathogenesis+of+lupus+nephritis+in+NZB/W+mice+and+the+effect+of+4-methylumbelliferone-
dc.identifier.emailYung, S: ssyyung@hku.hken_HK
dc.identifier.emailChan, DTM: dtmchan@hku.hken_HK
dc.identifier.authorityYung, S=rp00455en_HK
dc.identifier.authorityChan, DTM=rp00394en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1177/09612033100190010101-
dc.identifier.pmid20511279-
dc.identifier.scopuseid_2-s2.0-77953045627-
dc.identifier.hkuros172772en_HK
dc.identifier.volume19-
dc.identifier.issue1, suppl.-
dc.identifier.spage115-
dc.identifier.epage116-
dc.description.otherThe 9th International Congress on Systemic Lupus Erythematosus (SLE), Vancouver, Canada, 24-27 June 2010. In Lupus, 2010, v. 19 n. 1, suppl., p. 115-116, abstract no. PO1.M.4-

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