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-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.

中文翻译：

---

核心蛋白聚糖在腹膜透析和PD相关性腹膜炎中的抗纤维化作用。

背景技术进行性腹膜纤维化是长期腹膜透析（PD）患者的常见并发症。PD相关的腹膜炎是主要的恶化因素。我们调查了腹膜间皮细胞分泌的核心蛋白聚糖的抗纤维化特性。方法测定稳定的PD患者和腹膜炎患者的透析液除蛋白水平。进行了体外实验以研究核心蛋白聚糖在人腹膜间皮细胞（HPMC）纤维化反应中的作用。结果PD持续时间的增加与透析液甲壳素和CA125水平的逐渐降低有关。透析液核心蛋白水平与CA125水平相关。腹膜炎发作与透析液装饰蛋白的大量下降有关，尽管临床恢复，但这种情况持续了三个月以上。透析液核心蛋白水平与TGF-β1相关，但与IL-1β和IL-8呈负相关。TGF-β1，IL-1β，IL-6，IL-8或TNF-α减少HPMC中的核心蛋白聚糖分泌，但诱导纤连蛋白表达。这些作用部分地通过增加的p38 MAPK和AKT / PI3K磷酸化介导。Decorin通过降低TGF-βRI，p38 MAPK和AKT / PI3K磷酸化以及增加糖原合酶激酶-3β磷酸化，消除了PD液或促纤维化细胞因子对间皮细胞中纤连蛋白表达的诱导。在这些条件下，Decorin基因沉默导致纤连蛋白表达增加。解释我们的数据表明，当这些细胞经受腹膜透析液和PD中促纤维化细胞因子的促纤维化作用时，尤其是在腹膜炎期间，HPMC中的除芯蛋白具有抗纤维化作用。