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Conference Paper: Suppression of hyaluronan synthesis with 4-methylumbelliferone in NZB/W F1 mice is associated with reduced renal inflammation and renal function improvement

TitleSuppression of hyaluronan synthesis with 4-methylumbelliferone in NZB/W F1 mice is associated with reduced renal inflammation and renal function improvement
Authors
Issue Date2011
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Kidney Week 2011 - The 44th Annual Meeting of the American Society of Nephrology, Philadelphia, PA., 8-13 November 2011. In Journal of the American Society of Nephrology, 2011 meeting abstracts, p. 134A, TH-PO101 How to Cite?
AbstractBACKGROUND: We previously demonstrated that glomerular hyaluronan (HA) expression is increased in lupus nephritis, but its role in pathogenesis remains to be determined. This study investigated the effect of 4-methylumbelliferone, a specific inhibitor of HA synthesis, on disease manifestations in a lupus mouse model. METHODS: Female NZB/W F1 mice with established nephritis and proteinuria greater than 3g/l were randomized to receive treatment with sterile PBS, vehicle alone (1% Arabic Gum in PBS) or 4-methylumbelliferone in 1% Arabic Gum (MU, 3g/kg/day) for 2, 4, 8 and 12 weeks (n=6 for all time points for each group), after which the mice were sacrificed, blood collected and kidneys harvested for assessment of histology and expression of inflammatory mediators. Spot urine was obtained for the measurement of albumin-to-creatinine ratio. RESULTS: Serum HA levels increased in a time-dependent manner as disease progressed in PBS and vehicle treated mice. This was associated with increased periglomerular and tubulo-interstitial HA expression. MU treatment for 12 weeks reduced serum HA level by 30% and decreased renal HA expression to near normal levels. Urine albumin-to-creatinine ratio and serum levels of urea and creatinine increased in both PBS and vehicle treated mice with progressive disease, but were significantly decreased in mice after 12 weeks of MU treatment (P<0.05 for all, compared to both control groups). MU-treated mice also showed reduced glomerular deposition of IgG and C3, IL-6 and TNF-α expression, and glomerular infiltration by CD4+ T cells, CD19+ B cells and macrophages compared to controls. CONCLUSIONS: These results suggest that HA plays an important role in the pathogenesis of lupus nephritis and suppression of HA synthesis can ameliorate disease manifestations.
DescriptionBasic/Experimental Inflammation (Poster): TH-PO101
Abstract Supplement of JASN is located at http://www.asn-online.org/education/kidneyweek/archives/
Persistent Identifierhttp://hdl.handle.net/10722/160345
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorChan, DTMen_US
dc.contributor.authorTse, WWen_US
dc.contributor.authorChau, Men_US
dc.contributor.authorYung, Sen_US
dc.date.accessioned2012-08-16T06:08:09Z-
dc.date.available2012-08-16T06:08:09Z-
dc.date.issued2011en_US
dc.identifier.citationKidney Week 2011 - The 44th Annual Meeting of the American Society of Nephrology, Philadelphia, PA., 8-13 November 2011. In Journal of the American Society of Nephrology, 2011 meeting abstracts, p. 134A, TH-PO101en_US
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/160345-
dc.descriptionBasic/Experimental Inflammation (Poster): TH-PO101-
dc.descriptionAbstract Supplement of JASN is located at http://www.asn-online.org/education/kidneyweek/archives/-
dc.description.abstractBACKGROUND: We previously demonstrated that glomerular hyaluronan (HA) expression is increased in lupus nephritis, but its role in pathogenesis remains to be determined. This study investigated the effect of 4-methylumbelliferone, a specific inhibitor of HA synthesis, on disease manifestations in a lupus mouse model. METHODS: Female NZB/W F1 mice with established nephritis and proteinuria greater than 3g/l were randomized to receive treatment with sterile PBS, vehicle alone (1% Arabic Gum in PBS) or 4-methylumbelliferone in 1% Arabic Gum (MU, 3g/kg/day) for 2, 4, 8 and 12 weeks (n=6 for all time points for each group), after which the mice were sacrificed, blood collected and kidneys harvested for assessment of histology and expression of inflammatory mediators. Spot urine was obtained for the measurement of albumin-to-creatinine ratio. RESULTS: Serum HA levels increased in a time-dependent manner as disease progressed in PBS and vehicle treated mice. This was associated with increased periglomerular and tubulo-interstitial HA expression. MU treatment for 12 weeks reduced serum HA level by 30% and decreased renal HA expression to near normal levels. Urine albumin-to-creatinine ratio and serum levels of urea and creatinine increased in both PBS and vehicle treated mice with progressive disease, but were significantly decreased in mice after 12 weeks of MU treatment (P<0.05 for all, compared to both control groups). MU-treated mice also showed reduced glomerular deposition of IgG and C3, IL-6 and TNF-α expression, and glomerular infiltration by CD4+ T cells, CD19+ B cells and macrophages compared to controls. CONCLUSIONS: These results suggest that HA plays an important role in the pathogenesis of lupus nephritis and suppression of HA synthesis can ameliorate disease manifestations.-
dc.languageengen_US
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org-
dc.relation.ispartofJournal of the American Society of Nephrologyen_US
dc.titleSuppression of hyaluronan synthesis with 4-methylumbelliferone in NZB/W F1 mice is associated with reduced renal inflammation and renal function improvementen_US
dc.typeConference_Paperen_US
dc.identifier.emailChan, DTM: dtmchan@hku.hken_US
dc.identifier.emailTse, WW: kenniskt@hku.hken_US
dc.identifier.emailChau, M: melchau@hkucc.hku.hken_US
dc.identifier.emailYung, S: ssyyung@hku.hken_US
dc.identifier.authorityChan, DTM=rp00394en_US
dc.identifier.authorityYung, S=rp00455en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros205058en_US
dc.identifier.volume2011-
dc.identifier.issuemeeting abstracts-
dc.identifier.spage134A-
dc.identifier.epage134A-
dc.publisher.placeUnited States-

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