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Conference Paper: Decorin inhibits epithelial-to-mesenchymal transition and fibrogenesis in mesothelial cells through inhibition of MAPK phosphorylation

TitleDecorin inhibits epithelial-to-mesenchymal transition and fibrogenesis in mesothelial cells through inhibition of MAPK phosphorylation
Authors
Issue Date2013
PublisherThe International Society of Nephrology (ISN),.
Citation
World Congress of Nephrology (WCN), Hong Kong, China, 31 May-4 June 2013, abstract no. SA013 How to Cite?
AbstractINTRODUCTION AND AIMS: Peritoneal fibrosis is one of the most serious complications observed in patients on long-term peritoneal dialysis (PD) and is a major cause of technique failure. Mesothelial cells line the peritoneal cavity and contribute to peritoneal fibrosis through their synthesis of various growth factors and extracellular matrix components and their ability to undergo epithelial-to-mesenchymal transition (EMT). Mesothelial cells synthesize decorin, a dermatan sulfate proteoglycan with anti-fibrotic properties. In this study, we investigated the mechanisms through which decorin regulates EMT and fibrogenesis in mesothelial cells. METHODS: Confluent, growth arrested mesothelial cells were stimulated with exogenous TGF-β1, IL-1β and TNF-α - cytokines known to be increased in the peritoneal cavity during PD (10 ng/ml for both) in the presence or absence of specific inhibitors of ERK, p38 MAPK and JNK, or exogenous decorin (0-1000 ng/ml) for 24h. Cell morphology and expression of β-catenin, E-cadherin, snail and fibronectin, and phosphorylation of ERK, p38 MAPK and JNK was determined by phase contract microscopy and Western blot analysis respectively. RESULTS: Exogenous TGF-β1, IL-1β and TNF-α induced EMT in mesothelial cells. Phenotypic changes were accompanied by a decrease in E-cadherin, an increase in β-catenin, snail and fibronectin synthesis and phosphorylation of ERK, p38 MAPK and JNK. Incubation of mesothelial cells with PD98059, SB203580 and SP600125 - specific inhibitors to ERK, p38 MAPK and JNK respectively, demonstrated that all three signaling pathways contributed to induction of the EMT cascade and fibrogenesis in mesothelial cells. Incubation of cells with decorin inhibited EMT and fibronectin synthesis induced by TGF-β1, IL-1β and TNF-α (P<0.05, for all). The effect of decorin was mediated through the suppression of ERK, p38 MAPK and JNK phosphorylation. Gene silencing of decorin using RNAi resulted in the amplification of IL-1β induced fibronectin. CONCLUSIONS: Our data demonstrate that decorin can suppress EMT and fibrotic processes in mesothelial cells during PD through modulation of the MAPK signaling pathways.
DescriptionConferenc theme: Sustainability and Diversity
Moderated Poster Session: Cell Signaling, Cell Growth Control, Hormones and Cytokines
Persistent Identifierhttp://hdl.handle.net/10722/186842

 

DC FieldValueLanguage
dc.contributor.authorJiang, Nen_US
dc.contributor.authorYung, SSYen_US
dc.contributor.authorChau, KMen_US
dc.contributor.authorZhang, Qen_US
dc.contributor.authorChan, DTMen_US
dc.date.accessioned2013-08-20T12:21:13Z-
dc.date.available2013-08-20T12:21:13Z-
dc.date.issued2013en_US
dc.identifier.citationWorld Congress of Nephrology (WCN), Hong Kong, China, 31 May-4 June 2013, abstract no. SA013en_US
dc.identifier.urihttp://hdl.handle.net/10722/186842-
dc.descriptionConferenc theme: Sustainability and Diversity-
dc.descriptionModerated Poster Session: Cell Signaling, Cell Growth Control, Hormones and Cytokines-
dc.description.abstractINTRODUCTION AND AIMS: Peritoneal fibrosis is one of the most serious complications observed in patients on long-term peritoneal dialysis (PD) and is a major cause of technique failure. Mesothelial cells line the peritoneal cavity and contribute to peritoneal fibrosis through their synthesis of various growth factors and extracellular matrix components and their ability to undergo epithelial-to-mesenchymal transition (EMT). Mesothelial cells synthesize decorin, a dermatan sulfate proteoglycan with anti-fibrotic properties. In this study, we investigated the mechanisms through which decorin regulates EMT and fibrogenesis in mesothelial cells. METHODS: Confluent, growth arrested mesothelial cells were stimulated with exogenous TGF-β1, IL-1β and TNF-α - cytokines known to be increased in the peritoneal cavity during PD (10 ng/ml for both) in the presence or absence of specific inhibitors of ERK, p38 MAPK and JNK, or exogenous decorin (0-1000 ng/ml) for 24h. Cell morphology and expression of β-catenin, E-cadherin, snail and fibronectin, and phosphorylation of ERK, p38 MAPK and JNK was determined by phase contract microscopy and Western blot analysis respectively. RESULTS: Exogenous TGF-β1, IL-1β and TNF-α induced EMT in mesothelial cells. Phenotypic changes were accompanied by a decrease in E-cadherin, an increase in β-catenin, snail and fibronectin synthesis and phosphorylation of ERK, p38 MAPK and JNK. Incubation of mesothelial cells with PD98059, SB203580 and SP600125 - specific inhibitors to ERK, p38 MAPK and JNK respectively, demonstrated that all three signaling pathways contributed to induction of the EMT cascade and fibrogenesis in mesothelial cells. Incubation of cells with decorin inhibited EMT and fibronectin synthesis induced by TGF-β1, IL-1β and TNF-α (P<0.05, for all). The effect of decorin was mediated through the suppression of ERK, p38 MAPK and JNK phosphorylation. Gene silencing of decorin using RNAi resulted in the amplification of IL-1β induced fibronectin. CONCLUSIONS: Our data demonstrate that decorin can suppress EMT and fibrotic processes in mesothelial cells during PD through modulation of the MAPK signaling pathways.-
dc.languageengen_US
dc.publisherThe International Society of Nephrology (ISN),.-
dc.relation.ispartofWorld Congress of Nephrology (WCN)en_US
dc.titleDecorin inhibits epithelial-to-mesenchymal transition and fibrogenesis in mesothelial cells through inhibition of MAPK phosphorylationen_US
dc.typeConference_Paperen_US
dc.identifier.emailYung, SSY: ssyyung@hku.hken_US
dc.identifier.emailChau, KM: melchau@hkucc.hku.hken_US
dc.identifier.emailZhang, Q: zhjhr@hkucc.hku.hken_US
dc.identifier.emailChan, DTM: dtmchan@hku.hken_US
dc.identifier.authorityYung, SSY=rp00455en_US
dc.identifier.authorityChan, DTM=rp00394en_US
dc.identifier.hkuros220419en_US
dc.publisher.placeBelgium-

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