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


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

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Publications

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

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]

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