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Conference Paper: High glucose promotes renal tubular CTGF expression via the activation of protease-activated receptors
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TitleHigh glucose promotes renal tubular CTGF expression via the activation of protease-activated receptors
 
AuthorsYiu, WH
Leung, JCK
Chan, LYY
Lan, HY
Lai, KN
Tang, SCW
 
Issue Date2011
 
PublisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
 
CitationThe 44th Annual Meeting of the American Society of Nephrology (ASN), Philadelphia, PA., 8-13 November 2011. In Journal of the American Society of Nephrology, 2011, v. 22 n. abstract suppl., p. 713A, no. SA-PO2584 [How to Cite?]
 
AbstractBACKGROUND: Protease-Activated Receptors (PARs) are potent mediators of inflammation and fibrosis after being cleaved and activated by serine proteases. Overexpression of PARs in several kidney diseases suggests a possible role in the progression of kidney damage. Based on our previous study in which high glucose stimulates pro-inflammatory and pro-fibrotic signals in cultured human proximal tubular epithelial cells (PTEC), we here investigate the role of PARs in high glucose induced expression of connective tissue growth factor (CTGF), the pro-fibrotic mediator for the accumulation of extracellular matrix protein and the pathogenesis of diabetic nephropathy. METHODS: Human PTEC were cultured in medium with normal glucose (5mM), high glucose (30mM) or high glucose with specific PAR antagonist (SCH79797 for PAR-1, ENMD-1068 for PAR-2 and trans-Cinnamoyl-YPGKF-NH2 for PAR-4) added 1h before stimulation. RNA were isolated after 6h incubation for gene expression analysis by quantitative real time PCR and culture supernatant were collected after 24h incubation for protein expression analysis by ELISA. RESULTS: We demonstrated the expression of PARs in PTEC. PAR-2 was the most abundant receptor in PTEC compared to PAR-1 and PAR-4, whereas PAR-4 had the lowest expression among the receptor family. However, high glucose (30mM) selectively enhanced PAR-4, but not PAR-1 and PAR-2 mRNA expression in PTEC. In addition, high glucose stimulated a time-dependent increase in CTGF mRNA and protein levels, and the expression was significantly inhibited by pre-incubation with PAR-1, PAR-2 and PAR-4 antagonists. CONCLUSIONS: These results suggest that PARs mediate the modulation of CTGF expression in renal tubular cells and the up-regulation of PAR-4 may further contribute to the progression of fibrosis in the diabetic kidney.
 
DescriptionSession: Diabetic Nephropathy Basic - III: no. SA-PO2584
 
ISSN1046-6673
2012 Impact Factor: 8.987
2012 SCImago Journal Rankings: 4.397
 
DC FieldValue
dc.contributor.authorYiu, WH
 
dc.contributor.authorLeung, JCK
 
dc.contributor.authorChan, LYY
 
dc.contributor.authorLan, HY
 
dc.contributor.authorLai, KN
 
dc.contributor.authorTang, SCW
 
dc.date.accessioned2012-08-16T06:07:54Z
 
dc.date.available2012-08-16T06:07:54Z
 
dc.date.issued2011
 
dc.description.abstractBACKGROUND: Protease-Activated Receptors (PARs) are potent mediators of inflammation and fibrosis after being cleaved and activated by serine proteases. Overexpression of PARs in several kidney diseases suggests a possible role in the progression of kidney damage. Based on our previous study in which high glucose stimulates pro-inflammatory and pro-fibrotic signals in cultured human proximal tubular epithelial cells (PTEC), we here investigate the role of PARs in high glucose induced expression of connective tissue growth factor (CTGF), the pro-fibrotic mediator for the accumulation of extracellular matrix protein and the pathogenesis of diabetic nephropathy. METHODS: Human PTEC were cultured in medium with normal glucose (5mM), high glucose (30mM) or high glucose with specific PAR antagonist (SCH79797 for PAR-1, ENMD-1068 for PAR-2 and trans-Cinnamoyl-YPGKF-NH2 for PAR-4) added 1h before stimulation. RNA were isolated after 6h incubation for gene expression analysis by quantitative real time PCR and culture supernatant were collected after 24h incubation for protein expression analysis by ELISA. RESULTS: We demonstrated the expression of PARs in PTEC. PAR-2 was the most abundant receptor in PTEC compared to PAR-1 and PAR-4, whereas PAR-4 had the lowest expression among the receptor family. However, high glucose (30mM) selectively enhanced PAR-4, but not PAR-1 and PAR-2 mRNA expression in PTEC. In addition, high glucose stimulated a time-dependent increase in CTGF mRNA and protein levels, and the expression was significantly inhibited by pre-incubation with PAR-1, PAR-2 and PAR-4 antagonists. CONCLUSIONS: These results suggest that PARs mediate the modulation of CTGF expression in renal tubular cells and the up-regulation of PAR-4 may further contribute to the progression of fibrosis in the diabetic kidney.
 
dc.description.naturelink_to_OA_fulltext
 
dc.descriptionSession: Diabetic Nephropathy Basic - III: no. SA-PO2584
 
dc.identifier.citationThe 44th Annual Meeting of the American Society of Nephrology (ASN), Philadelphia, PA., 8-13 November 2011. In Journal of the American Society of Nephrology, 2011, v. 22 n. abstract suppl., p. 713A, no. SA-PO2584 [How to Cite?]
 
dc.identifier.epage713A
 
dc.identifier.hkuros202608
 
dc.identifier.issn1046-6673
2012 Impact Factor: 8.987
2012 SCImago Journal Rankings: 4.397
 
dc.identifier.issueabstract suppl.
 
dc.identifier.spage713A
 
dc.identifier.urihttp://hdl.handle.net/10722/160304
 
dc.identifier.volume22
 
dc.languageeng
 
dc.publisherAmerican Society of Nephrology. The Journal's web site is located at http://www.jasn.org
 
dc.publisher.placeUnited States
 
dc.relation.ispartofJournal of the American Society of Nephrology
 
dc.titleHigh glucose promotes renal tubular CTGF expression via the activation of protease-activated receptors
 
dc.typeConference_Paper
 
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<contributor.author>Chan, LYY</contributor.author>
<contributor.author>Lan, HY</contributor.author>
<contributor.author>Lai, KN</contributor.author>
<contributor.author>Tang, SCW</contributor.author>
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<description.abstract>BACKGROUND: Protease-Activated Receptors (PARs) are potent mediators of inflammation and fibrosis after being cleaved and activated by serine proteases. Overexpression of PARs in several kidney diseases suggests a possible role in the progression of kidney damage. Based on our previous study in which high glucose stimulates pro-inflammatory and pro-fibrotic signals in cultured human proximal tubular epithelial cells (PTEC), we here investigate the role of PARs in high glucose induced expression of connective tissue growth factor (CTGF), the pro-fibrotic mediator for the accumulation of extracellular matrix protein and the pathogenesis of diabetic nephropathy. METHODS: Human PTEC were cultured in medium with normal glucose (5mM), high glucose (30mM) or high glucose with specific PAR antagonist (SCH79797 for PAR-1, ENMD-1068 for PAR-2 and trans-Cinnamoyl-YPGKF-NH2 for PAR-4) added 1h before stimulation. RNA were isolated after 6h incubation for gene expression analysis by quantitative real time PCR and culture supernatant were collected after 24h incubation for protein expression analysis by ELISA. RESULTS: We demonstrated the expression of PARs in PTEC. PAR-2 was the most abundant receptor in PTEC compared to PAR-1 and PAR-4, whereas PAR-4 had the lowest expression among the receptor family. However, high glucose (30mM) selectively enhanced PAR-4, but not PAR-1 and PAR-2 mRNA expression in PTEC. In addition, high glucose stimulated a time-dependent increase in CTGF mRNA and protein levels, and the expression was significantly inhibited by pre-incubation with PAR-1, PAR-2 and PAR-4 antagonists. CONCLUSIONS: These results suggest that PARs mediate the modulation of CTGF expression in renal tubular cells and the up-regulation of PAR-4 may further contribute to the progression of fibrosis in the diabetic kidney.</description.abstract>
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