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Conference Paper: Comparison of mycophenolate mofetil and rapamycin on inflammatory and fibrotic mediators in NZB/W mice with active nephritis

TitleComparison of mycophenolate mofetil and rapamycin on inflammatory and fibrotic mediators in NZB/W mice with active nephritis
Authors
Issue Date2010
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
Citation
Renal Week 2010 - The 43rd Annual Meeting of the American Society of Nephrology, Denver, CO., 16-21 November 2010. In Journal of the American Society of Nephrology, 2010, meeting abstracts, p. 753A, SA-PO2804 How to Cite?
AbstractRapamycin might have a role in the treatment of lupus nephritis because of its immunosuppressive and anti-proliferative effect. This study compared the effect of rapamycin and mycophenolate mofetil (MMF) on inflammatory and fibrotic mediators in a murine lupus nephritis model. Female NZB/W mice with established nephritis and proteinuria >3g/L were randomized to receive treatment with vehicle alone (control), MMF (100mg/kg/d), or rapamycin (3mg/kg/d) for 2, 6 and 12 weeks (n=6 for all time points in each group), and clinical parameters and renal histology assessed. Albumin-to-creatinine ratio and circulating anti-DNA antibodies increased progressively in control mice, and these abnormalities were ameliorated in both MMF and rapamycin treated groups (P<0.01 for both compared to control mice after 12 weeks). Mice treated with MMF or rapamycin demonstrated reduced glomerular expansion (glomerular tuft area: 4252.15±324.15, 2645.76±564.21 and 2648.21±468.32μm2 for control, MMF and rapamycin respectively, P<0.01 for control vs MMF or rapamycin after 12 weeks treatment), and decreased interstitial fibrosis as well as tubular atrophy compared to control mice. Both MMF and rapamycin significantly reduced glomerular IgG and C3 deposition and this was associated with the abrogation of intra-glomerular expression of CD4, CD8, CD19 and MAC-1. Renal expression of IL-6, TGF-β1, fibronectin and collagen type I was reduced to near normal levels in MMF treated mice, whilst tubular expression of the aforementioned fibrotic markers was still significant in mice treated with rapamycin for 12 weeks. These results suggest that while both MMF and rapamycin ameliorate disease manifestations in lupus nephritis, rapamycin might be less effective in suppressing tubulointerstitial expression of fibrosis markers compared with MMF.
DescriptionImmunology, Pathology: Basic/Experimental Immunology I (Poster): SA-PO2804
Abstract Supplement of JASN is located at http://www.asn-online.org/education/kidneyweek/archives/
Persistent Identifierhttp://hdl.handle.net/10722/135920
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorChan, DTMen_US
dc.contributor.authorZhang, Cen_US
dc.contributor.authorChau, KMen_US
dc.contributor.authorYung, SSYen_US
dc.date.accessioned2011-07-27T01:59:43Z-
dc.date.available2011-07-27T01:59:43Z-
dc.date.issued2010en_US
dc.identifier.citationRenal Week 2010 - The 43rd Annual Meeting of the American Society of Nephrology, Denver, CO., 16-21 November 2010. In Journal of the American Society of Nephrology, 2010, meeting abstracts, p. 753A, SA-PO2804en_US
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/135920-
dc.descriptionImmunology, Pathology: Basic/Experimental Immunology I (Poster): SA-PO2804-
dc.descriptionAbstract Supplement of JASN is located at http://www.asn-online.org/education/kidneyweek/archives/-
dc.description.abstractRapamycin might have a role in the treatment of lupus nephritis because of its immunosuppressive and anti-proliferative effect. This study compared the effect of rapamycin and mycophenolate mofetil (MMF) on inflammatory and fibrotic mediators in a murine lupus nephritis model. Female NZB/W mice with established nephritis and proteinuria >3g/L were randomized to receive treatment with vehicle alone (control), MMF (100mg/kg/d), or rapamycin (3mg/kg/d) for 2, 6 and 12 weeks (n=6 for all time points in each group), and clinical parameters and renal histology assessed. Albumin-to-creatinine ratio and circulating anti-DNA antibodies increased progressively in control mice, and these abnormalities were ameliorated in both MMF and rapamycin treated groups (P<0.01 for both compared to control mice after 12 weeks). Mice treated with MMF or rapamycin demonstrated reduced glomerular expansion (glomerular tuft area: 4252.15±324.15, 2645.76±564.21 and 2648.21±468.32μm2 for control, MMF and rapamycin respectively, P<0.01 for control vs MMF or rapamycin after 12 weeks treatment), and decreased interstitial fibrosis as well as tubular atrophy compared to control mice. Both MMF and rapamycin significantly reduced glomerular IgG and C3 deposition and this was associated with the abrogation of intra-glomerular expression of CD4, CD8, CD19 and MAC-1. Renal expression of IL-6, TGF-β1, fibronectin and collagen type I was reduced to near normal levels in MMF treated mice, whilst tubular expression of the aforementioned fibrotic markers was still significant in mice treated with rapamycin for 12 weeks. These results suggest that while both MMF and rapamycin ameliorate disease manifestations in lupus nephritis, rapamycin might be less effective in suppressing tubulointerstitial expression of fibrosis markers compared with MMF.-
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.titleComparison of mycophenolate mofetil and rapamycin on inflammatory and fibrotic mediators in NZB/W mice with active nephritisen_US
dc.typeConference_Paperen_US
dc.identifier.emailChan, DTM: dtmchan@hku.hken_US
dc.identifier.emailZhang, C: juzhang@hku.hken_US
dc.identifier.emailChau, KM: melchau@hkucc.hku.hken_US
dc.identifier.emailYung, SSY: ssyyung@hku.hken_US
dc.identifier.authorityChan, DTM=rp00394en_US
dc.identifier.authorityYung, SSY=rp00455en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros188592en_US
dc.identifier.issuemeeting abstracts-
dc.identifier.spage753Aen_US
dc.identifier.epage753Aen_US
dc.publisher.placeUnited States-

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