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Article: Anti-fibrotic effect of decorin in peritoneal dialysis and PD-associated peritonitis

TitleAnti-fibrotic effect of decorin in peritoneal dialysis and PD-associated peritonitis
Authors
KeywordsPeritoneal dialysis
Peritonitis
Decorin
Inflammation
Fibrosis
Issue Date2020
PublisherElsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com
Citation
EBioMedicine, 2020, v. 52, p. article no. 102661 How to Cite?
AbstractBackground: Progressive peritoneal fibrosis is a common complication in patients on long-term peritoneal dialysis (PD). PD-associated peritonitis is a major exacerbating factor. We investigated the anti-fibrotic properties of decorin secreted by peritoneal mesothelial cells. Methods: Dialysate decorin level in stable PD patients and those with peritonitis was measured. In vitro experiments were conducted to investigate the effect of decorin in fibrotic response in human peritoneal mesothelial cells (HPMC). Findings: Increasing PD duration was associated with a progressive decrease of dialysate decorin and CA125 levels. Dialysate decorin level correlated with CA125 level. Peritonitis episodes were associated with a massive drop of dialysate decorin, which persisted for over three months despite clinical recovery. Dialysate decorin level correlated with that of TGF-β1, but was inversely related to IL-1β and IL-8. TGF-β1, IL-1β, IL-6, IL-8, or TNF-α reduced decorin secretion in HPMC, but induced fibronectin expression. The effects were mediated in part through increased p38 MAPK and AKT/PI3K phosphorylation. Decorin abrogated the induction of fibronectin expression in mesothelial cells by PD fluids or pro-fibrotic cytokines, through decreased TGF-βRI, p38 MAPK and AKT/PI3K phosphorylation and increased glycogen synthase kinase-3β phosphorylation. Decorin gene-silencing resulted in increased fibronectin expression under these conditions. Interpretation: Our data demonstrate anti-fibrotic actions of decorin in HPMC, when these cells are subjected to the pro-fibrotic effect of peritoneal dialysate and pro-fibrotic cytokines in PD, especially during peritonitis.
Persistent Identifierhttp://hdl.handle.net/10722/284981
ISSN
2023 Impact Factor: 9.7
2023 SCImago Journal Rankings: 3.193
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorJiang, N-
dc.contributor.authorZhang, Q-
dc.contributor.authorChau, MKM-
dc.contributor.authorYip, MS-
dc.contributor.authorLui, SL-
dc.contributor.authorLiu, S-
dc.contributor.authorChu, KM-
dc.contributor.authorNgan, HYS-
dc.contributor.authorChan, TM-
dc.contributor.authorYung, SY-
dc.date.accessioned2020-08-07T09:05:10Z-
dc.date.available2020-08-07T09:05:10Z-
dc.date.issued2020-
dc.identifier.citationEBioMedicine, 2020, v. 52, p. article no. 102661-
dc.identifier.issn2352-3964-
dc.identifier.urihttp://hdl.handle.net/10722/284981-
dc.description.abstractBackground: Progressive peritoneal fibrosis is a common complication in patients on long-term peritoneal dialysis (PD). PD-associated peritonitis is a major exacerbating factor. We investigated the anti-fibrotic properties of decorin secreted by peritoneal mesothelial cells. Methods: Dialysate decorin level in stable PD patients and those with peritonitis was measured. In vitro experiments were conducted to investigate the effect of decorin in fibrotic response in human peritoneal mesothelial cells (HPMC). Findings: Increasing PD duration was associated with a progressive decrease of dialysate decorin and CA125 levels. Dialysate decorin level correlated with CA125 level. Peritonitis episodes were associated with a massive drop of dialysate decorin, which persisted for over three months despite clinical recovery. Dialysate decorin level correlated with that of TGF-β1, but was inversely related to IL-1β and IL-8. TGF-β1, IL-1β, IL-6, IL-8, or TNF-α reduced decorin secretion in HPMC, but induced fibronectin expression. The effects were mediated in part through increased p38 MAPK and AKT/PI3K phosphorylation. Decorin abrogated the induction of fibronectin expression in mesothelial cells by PD fluids or pro-fibrotic cytokines, through decreased TGF-βRI, p38 MAPK and AKT/PI3K phosphorylation and increased glycogen synthase kinase-3β phosphorylation. Decorin gene-silencing resulted in increased fibronectin expression under these conditions. Interpretation: Our data demonstrate anti-fibrotic actions of decorin in HPMC, when these cells are subjected to the pro-fibrotic effect of peritoneal dialysate and pro-fibrotic cytokines in PD, especially during peritonitis.-
dc.languageeng-
dc.publisherElsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com-
dc.relation.ispartofEBioMedicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectPeritoneal dialysis-
dc.subjectPeritonitis-
dc.subjectDecorin-
dc.subjectInflammation-
dc.subjectFibrosis-
dc.titleAnti-fibrotic effect of decorin in peritoneal dialysis and PD-associated peritonitis-
dc.typeArticle-
dc.identifier.emailYip, MS: yms2011@hku.hk-
dc.identifier.emailLui, SL: sllui@hkucc.hku.hk-
dc.identifier.emailLiu, S: stephasl@hku.hk-
dc.identifier.emailChu, KM: chukm@hku.hk-
dc.identifier.emailNgan, HYS: hysngan@hkucc.hku.hk-
dc.identifier.emailChan, TM: dtmchan@hkucc.hku.hk-
dc.identifier.emailYung, SY: ssyyung@hku.hk-
dc.identifier.authorityLiu, S=rp00372-
dc.identifier.authorityChu, KM=rp00435-
dc.identifier.authorityNgan, HYS=rp00346-
dc.identifier.authorityChan, TM=rp00394-
dc.identifier.authorityYung, SY=rp00455-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.ebiom.2020.102661-
dc.identifier.pmid32062358-
dc.identifier.pmcidPMC7016379-
dc.identifier.scopuseid_2-s2.0-85079420504-
dc.identifier.hkuros311647-
dc.identifier.volume52-
dc.identifier.spagearticle no. 102661-
dc.identifier.epagearticle no. 102661-
dc.identifier.isiWOS:000515132200003-
dc.publisher.placeNetherlands-
dc.identifier.issnl2352-3964-

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