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

Szebeni, Beáta and Veres-Székely, Apor and Pap, Domonkos and Bokrossy, Péter and Varga, Zoltán and Gaál, Anikó and Mihály, Judith and Pállinger, Éva and Takács, István and Pajtók, Csenge and Bernáth, Mária and Reusz, S. György and Szabó, J. Attila and Vannay, Ádám (2024) Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-β- and PDGF-B-Mediated Fibrotic Processes. CELLS, 13. No. 605. ISSN 2073-4409

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Abstract

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.

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