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Conference Paper: Hyaluronan exacerbates renal fibrosis in NZB/W mice through increased monocyte chemoattractant protein-1 and transforming growth factor-β1 secretion by mesangial cells

TitleHyaluronan exacerbates renal fibrosis in NZB/W mice through increased monocyte chemoattractant protein-1 and transforming growth factor-β1 secretion by mesangial cells
Other TitlesHyaluronan exacerbates renal fibrosis in NZB/W mice through increased MCP-1 and TGF-β1 secretion by mesangial cells
Authors
Issue Date2013
PublisherAmerican Society of Nephrology. The abstract suppl.'s website is located at https://www.asn-online.org/abstracts/
Citation
The 2013 Annual Meeting and Scientific Exposition of the American Society of Nephrology (Kidney Week 2013), Atlanta, GA., 5-10 November 2013. In Journal of the American Society of Nephrology Abstract Supplement, 2013, p. 232A , abstract no. TH-PO572 How to Cite?
AbstractBACKGROUND: Lupus nephritis is characterized by the production of anti-dsDNA antibodies and immune-mediated renal injury leading to glomerular and tubulointerstitial fibrosis. We have previously demonstrated that circulating hyaluronan (HA) level and glomerular HA expression are increased in patients and lupus-prone mice with active lupus nephritis, and are associated with increased glomerular matrix protein accumulation. This study investigates the role of HA on disease manifestations and renal fibrogenesis in a murine model of lupus nephritis. METHODS: Pre-disease female NZB/W mice were randomized to receive sterile PBS or high molecular weight HA by tail-vein injection (1mg/ml, 200l) once weekly for periods up to 24 weeks, after which the mice were sacrificed, blood and urine collected, and kidneys harvested to assess renal histology and expression of fibrosis mediators. Mesangial cells were isolated from the renal cortex of NZB/W mice to investigate the mechanisms that mediate increased HA synthesis. RESULTS: Treatment of mice with HA had no effect on survival, proteinuria or antidsDNA antibody level compared to control mice, but was associated with increased glomerular IgG and C3 deposition, significantly increased glomerular and tubulointerstitial expression of HA receptor CD44, MCP-1, TGF- β1, fibronectin and collagen type I from 18 to 24 weeks. Exogenous HA for 24h had no effect on mesangial cell proliferation, but significantly increased CD44, HA synthase III, fibronectin, laminin and collagen synthesis, in part through the induction of MCP-1 and TGF- β1 secretion (P<0.01 for both). Stimulation of mesangial cells with exogenous MCP-1 and TGF-β1 significantly increased cell associated and secreted HA levels respectively (P<0.05 for both). CONCLUSIONS: These results suggest that HA plays a significant role in renal fibrosis of lupus nephritis by inducing MCP-1 and TGF- β1 secretion, which in turn increase HA synthesis resulting in a positive feedback loop that amplifies the fibrotic process.
DescriptionThursday Poster: TH-PO572
Persistent Identifierhttp://hdl.handle.net/10722/214856
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorYung, S-
dc.contributor.authorTse, WW-
dc.contributor.authorChau, MKM-
dc.contributor.authorChan, DTM-
dc.date.accessioned2015-08-21T11:58:53Z-
dc.date.available2015-08-21T11:58:53Z-
dc.date.issued2013-
dc.identifier.citationThe 2013 Annual Meeting and Scientific Exposition of the American Society of Nephrology (Kidney Week 2013), Atlanta, GA., 5-10 November 2013. In Journal of the American Society of Nephrology Abstract Supplement, 2013, p. 232A , abstract no. TH-PO572-
dc.identifier.issn1046-6673-
dc.identifier.urihttp://hdl.handle.net/10722/214856-
dc.descriptionThursday Poster: TH-PO572-
dc.description.abstractBACKGROUND: Lupus nephritis is characterized by the production of anti-dsDNA antibodies and immune-mediated renal injury leading to glomerular and tubulointerstitial fibrosis. We have previously demonstrated that circulating hyaluronan (HA) level and glomerular HA expression are increased in patients and lupus-prone mice with active lupus nephritis, and are associated with increased glomerular matrix protein accumulation. This study investigates the role of HA on disease manifestations and renal fibrogenesis in a murine model of lupus nephritis. METHODS: Pre-disease female NZB/W mice were randomized to receive sterile PBS or high molecular weight HA by tail-vein injection (1mg/ml, 200l) once weekly for periods up to 24 weeks, after which the mice were sacrificed, blood and urine collected, and kidneys harvested to assess renal histology and expression of fibrosis mediators. Mesangial cells were isolated from the renal cortex of NZB/W mice to investigate the mechanisms that mediate increased HA synthesis. RESULTS: Treatment of mice with HA had no effect on survival, proteinuria or antidsDNA antibody level compared to control mice, but was associated with increased glomerular IgG and C3 deposition, significantly increased glomerular and tubulointerstitial expression of HA receptor CD44, MCP-1, TGF- β1, fibronectin and collagen type I from 18 to 24 weeks. Exogenous HA for 24h had no effect on mesangial cell proliferation, but significantly increased CD44, HA synthase III, fibronectin, laminin and collagen synthesis, in part through the induction of MCP-1 and TGF- β1 secretion (P<0.01 for both). Stimulation of mesangial cells with exogenous MCP-1 and TGF-β1 significantly increased cell associated and secreted HA levels respectively (P<0.05 for both). CONCLUSIONS: These results suggest that HA plays a significant role in renal fibrosis of lupus nephritis by inducing MCP-1 and TGF- β1 secretion, which in turn increase HA synthesis resulting in a positive feedback loop that amplifies the fibrotic process.-
dc.languageeng-
dc.publisherAmerican Society of Nephrology. The abstract suppl.'s website is located at https://www.asn-online.org/abstracts/-
dc.relation.ispartofJournal of the American Society of Nephrology Abstract Supplement-
dc.titleHyaluronan exacerbates renal fibrosis in NZB/W mice through increased monocyte chemoattractant protein-1 and transforming growth factor-β1 secretion by mesangial cells-
dc.title.alternativeHyaluronan exacerbates renal fibrosis in NZB/W mice through increased MCP-1 and TGF-β1 secretion by mesangial cells-
dc.typeConference_Paper-
dc.identifier.emailYung, S: ssyyung@hku.hk-
dc.identifier.emailTse, WW: kenniskt@hku.hk-
dc.identifier.emailChau, MKM: melchau@hku.hk-
dc.identifier.emailChan, DTM: dtmchan@hkucc.hku.hk-
dc.identifier.authorityYung, S=rp00455-
dc.identifier.authorityChan, DTM=rp00394-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros247474-
dc.identifier.spage232A , abstract no. TH-PO572-
dc.identifier.epage232A , abstract no. TH-PO572-
dc.publisher.placeUnited States-

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