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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
Title | Hyaluronan exacerbates renal fibrosis in NZB/W mice through increased monocyte chemoattractant protein-1 and transforming growth factor-β1 secretion by mesangial cells |
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Other Titles | Hyaluronan exacerbates renal fibrosis in NZB/W mice through increased MCP-1 and TGF-β1 secretion by mesangial cells |
Authors | |
Issue Date | 2013 |
Publisher | American 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? |
Abstract | BACKGROUND: 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, 200l) 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. |
Description | Thursday Poster: TH-PO572 |
Persistent Identifier | http://hdl.handle.net/10722/214856 |
ISSN | 2023 Impact Factor: 10.3 2023 SCImago Journal Rankings: 3.409 |
DC Field | Value | Language |
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dc.contributor.author | Yung, S | - |
dc.contributor.author | Tse, WW | - |
dc.contributor.author | Chau, MKM | - |
dc.contributor.author | Chan, DTM | - |
dc.date.accessioned | 2015-08-21T11:58:53Z | - |
dc.date.available | 2015-08-21T11:58:53Z | - |
dc.date.issued | 2013 | - |
dc.identifier.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 | - |
dc.identifier.issn | 1046-6673 | - |
dc.identifier.uri | http://hdl.handle.net/10722/214856 | - |
dc.description | Thursday Poster: TH-PO572 | - |
dc.description.abstract | BACKGROUND: 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, 200l) 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.language | eng | - |
dc.publisher | American Society of Nephrology. The abstract suppl.'s website is located at https://www.asn-online.org/abstracts/ | - |
dc.relation.ispartof | Journal of the American Society of Nephrology Abstract Supplement | - |
dc.title | Hyaluronan exacerbates renal fibrosis in NZB/W mice through increased monocyte chemoattractant protein-1 and transforming growth factor-β1 secretion by mesangial cells | - |
dc.title.alternative | Hyaluronan exacerbates renal fibrosis in NZB/W mice through increased MCP-1 and TGF-β1 secretion by mesangial cells | - |
dc.type | Conference_Paper | - |
dc.identifier.email | Yung, S: ssyyung@hku.hk | - |
dc.identifier.email | Tse, WW: kenniskt@hku.hk | - |
dc.identifier.email | Chau, MKM: melchau@hku.hk | - |
dc.identifier.email | Chan, DTM: dtmchan@hkucc.hku.hk | - |
dc.identifier.authority | Yung, S=rp00455 | - |
dc.identifier.authority | Chan, DTM=rp00394 | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.hkuros | 247474 | - |
dc.identifier.spage | 232A , abstract no. TH-PO572 | - |
dc.identifier.epage | 232A , abstract no. TH-PO572 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 1046-6673 | - |