Decorin ameliorates peritoneal fibrosis in peritoneal dialysis related peritonitis

Abstract

BACKGROUND: Peritonitis is a leading cause of peritoneal membrane failure in patients on peritoneal dialysis (PD). Decorin is a dermatan sulfate proteoglycan that possesses anti-fibrotic properties. Its role in peritoneal fibrosis remains to be fully defined. This study examined the relationship between dialysate decorin level and that of pro-infl amatory and fibrotic mediators in patients with PD associated peritonitis, and investigated the role of decorin in fibrogenesis. METHODS: Serial PD fluid samples were collected from 43 patients with PD related peritonitis. Dialysate samples from 23 PD patients without peritonitis in the past 12 months were included as controls. Dialysate concentrations of decorin, TGF-β1, IL-1β, IL-6 and IL-8 were measured using commercially available ELISAs. Mesothelial cells were incubated with spent PD fluid in the presence or absence of exogenous decorin, and the expression of SNAIL and fibronectin assessed. RESULTS: Dialysate decorin level was significantly higher at the onset of peritonitis compared to non-peritonitis dialysate (6345.23±1169.38 versus 257.6±26.9 pg/ml, P<0.05). Decorin level peaked 3 days after the onset of peritonitis and remained significantly higher than non-peritonitis levels 3 months later (8729.14±1145.21 pg/ml, P<0.05). Dialysate decorin levels showed an inverse relationship with dialysate IL-1β, IL-6 and IL-8 levels (r= -0.34, -0.38 and -0.32 respectively, P<0.05 for all), but correlated with TGF-β1 levels (r= 0.31, P<0.05). Peritoneal dialysate obtained at the onset of peritonitis significantly induced SNAIL and fibronectin synthesis in mesothelial cells, and this induction was reduced by exogenous decorin. SNAIL, but not fibronectin, expression inversely correlated with dialysate decorin level (r= -0.46, P=0.0024). CONCLUSIONS: Our data suggested a role of decorin in ameliorating the peritoneal fibrotic process induced by peritonitis, and that decorin may suppress epithelial-to-mesenchymal transition and fibrogenesis in peritoneal mesothelial cells.