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Article: Distinct effects of mycophenolate mofetil and cyclophosphamide on renal fibrosis in NZBWF1/J mice

TitleDistinct effects of mycophenolate mofetil and cyclophosphamide on renal fibrosis in NZBWF1/J mice
Authors
Issue Date2015
PublisherInforma Healthcare. The Journal's web site is located at http://www.tandf.co.uk/journals/titles/08916934.asp
Citation
Autoimmunity, 2015, p. in press How to Cite?
AbstractProgression to chronic renal failure varies between patients with lupus nephritis. We compared the effects of mycophenolate mofetil (MMF) and cyclophosphamide (CTX), on renal histology and cellular pathways of fibrosis in murine lupus nephritis. Female NZBWF1/J mice were randomized to treatment with vehicle, methylprednisolone (MP) alone, MMF + MP or CTX + MP for up to 12 weeks, and the effects on clinical parameters, renal histology, and fibrotic processes were investigated. Treatment with MMF + MP or CTX + MP both improved survival, renal function, and decreased anti-dsDNA antibody level and immune complex deposition in kidneys of mice with active nephritis. Vehicle-treated mice showed progressive increase in mesangial proliferation, inflammatory cell infiltration and renal tubular atrophy, associated with PKC-α activation, increased TGF-β1 expression and increased matrix protein deposition. MP treatment alone did not have any significant effect. MMF + MP or CTX + MP treatment for 12 weeks reduced these abnormalities. MMF + MP was more effective than CTX + MP in suppressing fibrotic mediators, histological fibrosis score and expression of TGF-β1, fibronectin and collagen I in the kidney. Results from in vitro experiments on human mesangial cells (HMC) showed that mycophenolic acid (MPA) was more effective than CTX in suppressing PKC-α activation and TGF-β1 secretion induced by human polyclonal anti-dsDNA antibodies. While both MPA and CTX decreased TGF-β1- and TNF-α-induced fibronectin synthesis, only MPA decreased IL-6 induced fibronectin synthesis. MPA and CTX show distinct effects on fibrotic and inflammatory processes in NZBWF1/J murine lupus nephritis, suggesting that MMF + MP may be more effective than CTX + MP in preserving normal renal histology in lupus nephritis.
Persistent Identifierhttp://hdl.handle.net/10722/214345
ISSN
2015 Impact Factor: 2.917
2015 SCImago Journal Rankings: 0.773

 

DC FieldValueLanguage
dc.contributor.authorYung, SSY-
dc.contributor.authorZhang, Q-
dc.contributor.authorChau, MKM-
dc.contributor.authorChan, DTM-
dc.date.accessioned2015-08-21T11:17:06Z-
dc.date.available2015-08-21T11:17:06Z-
dc.date.issued2015-
dc.identifier.citationAutoimmunity, 2015, p. in press-
dc.identifier.issn0891-6934-
dc.identifier.urihttp://hdl.handle.net/10722/214345-
dc.description.abstractProgression to chronic renal failure varies between patients with lupus nephritis. We compared the effects of mycophenolate mofetil (MMF) and cyclophosphamide (CTX), on renal histology and cellular pathways of fibrosis in murine lupus nephritis. Female NZBWF1/J mice were randomized to treatment with vehicle, methylprednisolone (MP) alone, MMF + MP or CTX + MP for up to 12 weeks, and the effects on clinical parameters, renal histology, and fibrotic processes were investigated. Treatment with MMF + MP or CTX + MP both improved survival, renal function, and decreased anti-dsDNA antibody level and immune complex deposition in kidneys of mice with active nephritis. Vehicle-treated mice showed progressive increase in mesangial proliferation, inflammatory cell infiltration and renal tubular atrophy, associated with PKC-α activation, increased TGF-β1 expression and increased matrix protein deposition. MP treatment alone did not have any significant effect. MMF + MP or CTX + MP treatment for 12 weeks reduced these abnormalities. MMF + MP was more effective than CTX + MP in suppressing fibrotic mediators, histological fibrosis score and expression of TGF-β1, fibronectin and collagen I in the kidney. Results from in vitro experiments on human mesangial cells (HMC) showed that mycophenolic acid (MPA) was more effective than CTX in suppressing PKC-α activation and TGF-β1 secretion induced by human polyclonal anti-dsDNA antibodies. While both MPA and CTX decreased TGF-β1- and TNF-α-induced fibronectin synthesis, only MPA decreased IL-6 induced fibronectin synthesis. MPA and CTX show distinct effects on fibrotic and inflammatory processes in NZBWF1/J murine lupus nephritis, suggesting that MMF + MP may be more effective than CTX + MP in preserving normal renal histology in lupus nephritis.-
dc.languageeng-
dc.publisherInforma Healthcare. The Journal's web site is located at http://www.tandf.co.uk/journals/titles/08916934.asp-
dc.relation.ispartofAutoimmunity-
dc.rightsAutoimmunity. Copyright © Informa Healthcare.-
dc.titleDistinct effects of mycophenolate mofetil and cyclophosphamide on renal fibrosis in NZBWF1/J mice-
dc.typeArticle-
dc.identifier.emailYung, SSY: ssyyung@hku.hk-
dc.identifier.emailZhang, Q: zhjhr@hkucc.hku.hk-
dc.identifier.emailChau, MKM: melchau@hkucc.hku.hk-
dc.identifier.emailChan, DTM: dtmchan@hkucc.hku.hk-
dc.identifier.authorityYung, SSY=rp00455-
dc.identifier.authorityChan, DTM=rp00394-
dc.identifier.doi10.3109/08916934.2015.1054027-
dc.identifier.pmid26099989-
dc.identifier.hkuros247447-
dc.identifier.spagein press-
dc.identifier.epagein press-
dc.publisher.placeUnited Kingdom-

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