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Conference Paper: Thrombospondin-1 induced by high glucose concentration mediates fibronectin synthesis in proximal renal tubular epithelial cells through both TGF-beta1 dependent and TGF-beta1 independent pathways

TitleThrombospondin-1 induced by high glucose concentration mediates fibronectin synthesis in proximal renal tubular epithelial cells through both TGF-beta1 dependent and TGF-beta1 independent pathways
Authors
Issue Date2005
PublisherAmerican Society of Nephrology. The abstract suppl.'s website is located at https://www.asn-online.org/abstracts/
Citation
The 38th Annual Meeting and Scientific Exposition of the American Society of Nephrology (ASN Renal Week 2005), Pennsylvania, PA., 8-13 November 2005. In Journal of the American Society of Nephrology Abstract Supplement, 2005, v. 16, p. 662A, abstract no. SA-PO480 How to Cite?
AbstractDiabetic nephropathy (DN) is a major cause of endstage renal disease. Much of the research on DN to date has focused on glomerular abnormalities, and yet the progression of renal failure correlates with tubulointerstitial damage. We investigated the mechanisms of increased fibronectin and TGF-β1 synthesis in human proximal renal tubular epithelial cells (PTEC) upon exposure to high glucose concentrations. PTEC were pre-conditioned with physiological (5mM) or elevated (10mM, 20mM and 30mM) D-glucose concentrations for up to 3 weeks, with mannitol as the hexose control. Elevated glucose concentrations increased secreted and cell-associated thrombospondin-1 (TSP-1) in a time- and dose-dependent manner (p<0.05 compared to 5mM D-glucose), which preceded TGF-β1 bioactivation and the induction of fibronectin synthesis. To investigate the role of TSP-1 in matrix synthesis by PTEC, cells were stimulated for 24 h with varying concentrations of exogenous TSP-1 (0-10 ng/ml). Maximum induction of TGF-β1 mRNA, secretion and bioactivation was observed with 0.1ng/ml TSP-1. TSP-1 did not modulate fibronectin gene expression, but induced its secretion and extracellular deposition in a dose-dependent manner (p<0.05 compared to control). TGF-β neutralizing antibody (0-10 μg/ml) by itself did not alter constitutive fibronectin synthesis in PTEC, but co-incubation of cells with TGF-β1 neutralizing antibody and TSP-1 resulted in a 25.7±2.7% inhibition of fibronectin deposition. The inhibition remained incomplete despite adding higher concentrations of TGF-β1 neutralizing antibody. TGF-β1 in turn modulated TSP-1 synthesis. Our results showed that induction of TSP-1 by a high glucose environment mediates the increased fibronectin secretion by PTEC. Only part of the downstream mechanisms are TGF-β1 dependent, and autocrine interactions may exist between TSP-1 and TGF-β1.
Persistent Identifierhttp://hdl.handle.net/10722/102528
ISSN
2015 Impact Factor: 8.491
2015 SCImago Journal Rankings: 4.699

 

DC FieldValueLanguage
dc.contributor.authorYung, SSYen_HK
dc.contributor.authorLee, YYCen_HK
dc.contributor.authorZhang, Qen_HK
dc.contributor.authorTsang, RCWen_HK
dc.contributor.authorChan, DTMen_HK
dc.date.accessioned2010-09-25T20:34:18Z-
dc.date.available2010-09-25T20:34:18Z-
dc.date.issued2005en_HK
dc.identifier.citationThe 38th Annual Meeting and Scientific Exposition of the American Society of Nephrology (ASN Renal Week 2005), Pennsylvania, PA., 8-13 November 2005. In Journal of the American Society of Nephrology Abstract Supplement, 2005, v. 16, p. 662A, abstract no. SA-PO480en_HK
dc.identifier.issn1046-6673en_HK
dc.identifier.urihttp://hdl.handle.net/10722/102528-
dc.description.abstractDiabetic nephropathy (DN) is a major cause of endstage renal disease. Much of the research on DN to date has focused on glomerular abnormalities, and yet the progression of renal failure correlates with tubulointerstitial damage. We investigated the mechanisms of increased fibronectin and TGF-β1 synthesis in human proximal renal tubular epithelial cells (PTEC) upon exposure to high glucose concentrations. PTEC were pre-conditioned with physiological (5mM) or elevated (10mM, 20mM and 30mM) D-glucose concentrations for up to 3 weeks, with mannitol as the hexose control. Elevated glucose concentrations increased secreted and cell-associated thrombospondin-1 (TSP-1) in a time- and dose-dependent manner (p<0.05 compared to 5mM D-glucose), which preceded TGF-β1 bioactivation and the induction of fibronectin synthesis. To investigate the role of TSP-1 in matrix synthesis by PTEC, cells were stimulated for 24 h with varying concentrations of exogenous TSP-1 (0-10 ng/ml). Maximum induction of TGF-β1 mRNA, secretion and bioactivation was observed with 0.1ng/ml TSP-1. TSP-1 did not modulate fibronectin gene expression, but induced its secretion and extracellular deposition in a dose-dependent manner (p<0.05 compared to control). TGF-β neutralizing antibody (0-10 μg/ml) by itself did not alter constitutive fibronectin synthesis in PTEC, but co-incubation of cells with TGF-β1 neutralizing antibody and TSP-1 resulted in a 25.7±2.7% inhibition of fibronectin deposition. The inhibition remained incomplete despite adding higher concentrations of TGF-β1 neutralizing antibody. TGF-β1 in turn modulated TSP-1 synthesis. Our results showed that induction of TSP-1 by a high glucose environment mediates the increased fibronectin secretion by PTEC. Only part of the downstream mechanisms are TGF-β1 dependent, and autocrine interactions may exist between TSP-1 and TGF-β1.-
dc.languageengen_HK
dc.publisherAmerican Society of Nephrology. The abstract suppl.'s website is located at https://www.asn-online.org/abstracts/en_HK
dc.relation.ispartofJournal of the American Society of Nephrology Abstract Supplementen_HK
dc.rightsJournal of the American Society of Nephrology. Copyright © Lippincott Williams & Wilkins.en_HK
dc.titleThrombospondin-1 induced by high glucose concentration mediates fibronectin synthesis in proximal renal tubular epithelial cells through both TGF-beta1 dependent and TGF-beta1 independent pathwaysen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1046-6673&volume=16&spage=662A&epage=&date=2005&atitle=Thrombospondin-1+Induced+by+High+Glucose+Concentration+Mediates+Fibronectin+Synthesis+in+Proximal+Renal+Tubular+Epithelial+Cells+Through+Both+TGF-beta1+Dependent+and+TGF-beta1+Independent+Pathwaysen_HK
dc.identifier.emailYung, SSY: ssyyung@hku.hken_HK
dc.identifier.emailChan, DTM: dtmchan@hku.hken_HK
dc.identifier.authorityYung, SSY=rp00455en_HK
dc.identifier.authorityChan, DTM=rp00394en_HK
dc.identifier.hkuros112137en_HK
dc.identifier.volume16en_HK
dc.identifier.spage662A, abstract no. SA-PO480en_HK
dc.identifier.epage662A, abstract no. SA-PO480-

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