Exploring the Regulatory Role of Heparanase in Peritoneal Fibrosis via the HPA/SDC-1/TGF-β Axis.

Peritoneal fibrosis (PF) is a serious complication in patients undergoing peritoneal dialysis (PD). Heparanase (HPA) may drive the progression of PF by promoting inflammation and tissue remodeling. This study aimed to evaluate HPA expression in peritoneal dialysate from end-stage renal disease (ESRD) patients receiving PD and to assess the correlation between HPA and fibrosis markers in PF. Peritoneal dialysate samples from ESRD patients were collected to measure HPA, syndecan-1 (SDC-1), and fibrosis markers. To further investigate the regulatory role of HPA in PF, a mouse model was established. Then mice were divided into four groups (n = 6 per group): control, PF, PF + HPSEi, and PF + Bailing groups. Tissue samples were collected for the detection of HPA, SDC-1, and fibrosis markers using RT-qPCR and Western blot. Fibrosis was evaluated via H&E and Masson staining. In peritoneal dialysate from 104 participants, HPA levels were positively correlated with SDC-1 (r = 0.617), TGF-β (r = 0.413), fibronectin (r = 0.278), and collagen I (r = 0.276). HPA (β = 0.0024), SDC-1 (β = 0.0572), TGF-β (β = 0.4358), and collagen I (β = 0.0023) were positively correlated with dialysis duration (all p < 0.05). Additionally, HPA was associated with high peritoneal transport function (p = 0.043). In mouse tissues, HPA inhibitor treatment downregulated TGF-β1, α-SMA, collagen I, and SDC-1, while upregulated E-cadherin expression and reducing tissue fibrosis. These effects were similar to those observed in the Bailing treatment group (all p < 0.05). HPA is positively correlated with SDC-1 and fibrosis markers. Inhibition of HPA attenuates PF, potentially through the HPA/SDC-1/TGF-β axis.