Ontology highlight
ABSTRACT: Background
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-?1, but was inversely related to IL-1? and IL-8. TGF-?1, IL-1?, IL-6, IL-8, or TNF-? 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-?RI, p38 MAPK and AKT/PI3K phosphorylation and increased glycogen synthase kinase-3? 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.
SUBMITTER: Jiang N
PROVIDER: S-EPMC7016379 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Jiang Na N Zhang Qing Q Chau Mel Km MK Yip Ming S MS Lui Sing Leung SL Liu Stephanie S Chu Kent Man KM Ngan Hextan Ys HY Chan Tak Mao TM Yung Susan S
EBioMedicine 20200212
<h4>Background</h4>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.<h4>Methods</h4>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 m ...[more]