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2-deoxy-glucose ameliorates the peritoneal mesothelial and endothelial barrier function perturbation occurring due to peritoneal dialysis fluids exposure

Peritoneal dialysis (PD) and prolonged exposure to PD fluids (PDF) induce peritoneal membrane (PM) fibrosis and hypervascularity, leading to functional PM degeneration. 2-deoxy-glucose (2-DG) has shown potential as PM antifibrotic by inhibiting hyper-glycolysis induced mesothelial-to-mesenchymal tra...

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Main Authors: Pitaraki, Eleanna (Author) , Jagirdar, Rajesh M. (Author) , Rouka, Erasmia (Author) , Bartosova, Maria (Author) , Sinis, Sotirios I. (Author) , Gourgoulianis, Konstantinos I. (Author) , Eleftheriadis, Theodoros (Author) , Stefanidis, Ioannis (Author) , Liakopoulos, Vassilios (Author) , Hatzoglou, Chrissi (Author) , Schmitt, Claus P. (Author) , Zarogiannis, Sotirios G. (Author)
Format: Article (Journal)
Language:English
Published: January 2024
In: Biochemical and biophysical research communications
Year: 2024, Volume: 693, Pages: 1-12
ISSN:1090-2104
DOI:10.1016/j.bbrc.2023.149376
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.bbrc.2023.149376
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0006291X23014705
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Author Notes:Eleanna Pitaraki, Rajesh M. Jagirdar, Erasmia Rouka, Maria Bartosova, Sotirios I. Sinis, Konstantinos I. Gourgoulianis, Theodoros Eleftheriadis, Ioannis Stefanidis, Vassilios Liakopoulos, Chrissi Hatzoglou, Claus Peter Schmitt, Sotirios G. Zarogiannis
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Summary:Peritoneal dialysis (PD) and prolonged exposure to PD fluids (PDF) induce peritoneal membrane (PM) fibrosis and hypervascularity, leading to functional PM degeneration. 2-deoxy-glucose (2-DG) has shown potential as PM antifibrotic by inhibiting hyper-glycolysis induced mesothelial-to-mesenchymal transition (MMT). We investigated whether administration of 2-DG with several PDF affects the permeability of mesothelial and endothelial barrier of the PM. The antifibrotic effect of 2-DG was confirmed by the gel contraction assay with embedded mesothelial (MeT-5A) or endothelial (EA.hy926) cells cultured in Dianeal® 2.5 % (CPDF), BicaVera® 2.3 % (BPDF), Balance® 2.3 % (LPDF) with/without 2-DG addition (0.2 mM), and qPCR for αSMA, CDH2 genes. Moreover, 2-DG effect was tested on the permeability of monolayers of mesothelial and endothelial cells by monitoring the transmembrane resistance (RTM), FITC-dextran (10, 70 kDa) diffusion and mRNA expression levels of CLDN-1 to -5, ZO1, SGLT1, and SGLT2 genes. Contractility of MeT-5A cells in CPDF/2-DG was decreased, accompanied by αSMA (0.17 ± 0.03) and CDH2 (2.92 ± 0.29) gene expression fold changes. Changes in αSMA, CDH2 were found in EA.hy926 cells, though αSMA also decreased under LPDF/2-DG incubation (0.42 ± 0.02). Overall, 2-DG mitigated the PDF-induced alterations in mesothelial and endothelial barrier function as shown by RTM, dextran transport and expression levels of the CLDN-1 to -5, ZO1, and SGLT2. Thus, supplementation of PDF with 2-DG not only reduces MMT but also improves functional permeability characteristics of the PM mesothelial and endothelial barrier.
Item Description:Online veröffentlicht 13 December 2023
Gesehen am 10.06.2024
Physical Description:Online Resource
ISSN:1090-2104
DOI:10.1016/j.bbrc.2023.149376

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