Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-β- and PDGF-B-Mediated Fibrotic Processes

• Published in: Cells (Basel, Switzerland) Switzerland), 2024-04, Vol.13 (7), p.605
• Main Authors: Szebeni, Beáta, Veres-Székely, Apor, Pap, Domonkos, Bokrossy, Péter, Varga, Zoltán, Gaál, Anikó, Mihály, Judith, Pállinger, Éva, Takács, István M, Pajtók, Csenge, Bernáth, Mária, Reusz, György S, Szabó, Attila J, Vannay, Ádám
• Format: Article
• Language: English
• Subjects: Animals; Biopsy; Care and treatment; CD63 antigen; Cell culture; Cell organelles; Cell proliferation; Child; Chlorhexidine; Collagen; Collagen - metabolism; Complications and side effects; Continuous ambulatory peritoneal dialysis; Development and progression; Experiments; Extracellular Vesicles; Fibroblasts; Fibrosis; Fourier transforms; Health aspects; Humans; Invoices; mesenchymal transition; Mice; Patients; Penicillin; Peritoneal dialysis; Peritoneal Dialysis - adverse effects; Peritoneal Fibrosis - metabolism; Peritoneal Fibrosis - pathology; Peritoneum; Platelet-derived growth factor; Proteins; Renal replacement therapy; Risk factors; Sclerosis; therapy; Transforming Growth Factor beta - metabolism; Transforming growth factor-b; Transforming growth factors
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells13070605

Among patients on peritoneal dialysis (PD), 50-80% will develop peritoneal fibrosis, and 0.5-4.4% will develop life-threatening encapsulating peritoneal sclerosis (EPS). Here, we investigated the role of extracellular vesicles (EVs) on the TGF-β- and PDGF-B-driven processes of peritoneal fibrosis. EVs were isolated from the peritoneal dialysis effluent (PDE) of children receiving continuous ambulatory PD. The impact of PDE-EVs on the epithelial-mesenchymal transition (EMT) and collagen production of the peritoneal mesothelial cells and fibroblasts were investigated in vitro and in vivo in the chlorhexidine digluconate (CG)-induced mice model of peritoneal fibrosis. PDE-EVs showed spherical morphology in the 100 nm size range, and their spectral features, CD63, and annexin positivity were characteristic of EVs. PDE-EVs penetrated into the peritoneal mesothelial cells and fibroblasts and reduced their PDE- or PDGF-B-induced proliferation. Furthermore, PDE-EVs inhibited the PDE- or TGF-β-induced EMT and collagen production of the investigated cell types. PDE-EVs contributed to the mesothelial layer integrity and decreased the submesothelial thickening of CG-treated mice. We demonstrated that PDE-EVs significantly inhibit the PDGF-B- or TGF-β-induced fibrotic processes in vitro and in vivo, suggesting that EVs may contribute to new therapeutic strategies to treat peritoneal fibrosis and other fibroproliferative diseases.