The dipeptide alanyl-glutamine ameliorates peritoneal fibrosis and attenuates IL-17 dependent pathways during peritoneal dialysis
| Autor: | Eelco D. Keuning, Manuel López-Cabrera, Evelina Ferrantelli, Marc Vila Cuenca, Georgios Liappas, Thomas L. Foster, Robert H.J. Beelen, Marc G. Vervloet |
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| Přispěvatelé: | Molecular cell biology and Immunology, AII - Inflammatory diseases, Physiology, Nephrology, ICaR - Circulation and metabolism |
| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Epithelial-Mesenchymal Transition Angiogenesis medicine.medical_treatment 030232 urology & nephrology Inflammation Pharmacology Protective Agents Peritoneal dialysis 03 medical and health sciences 0302 clinical medicine Peritoneum Fibrosis Animals Medicine Rats Wistar Peritoneal Fibrosis Neovascularization Pathologic business.industry Interleukin-17 Dipeptides medicine.disease Extracellular Matrix Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cytoprotection Nephrology Immunology Female Interleukin 17 Inflammation Mediators medicine.symptom business Peritoneal Dialysis Biomarkers Signal Transduction Transforming growth factor |
| Zdroj: | Kidney International, 89(3), 625-635. Nature Publishing Group Ferrantelli, E, Liappas, G, Cuenca, M V, Keuning, E D, Foster, T L, Vervloet, M G, Lopez-Cabrera, M & Beelen, R H J 2016, ' The dipeptide alanyl-glutamine ameliorates peritoneal fibrosis and attenuates IL-17 dependent pathways during peritoneal dialysis ', Kidney International, vol. 89, no. 3, pp. 625-635 . https://doi.org/10.1016/j.kint.2015.12.005 |
| ISSN: | 0085-2538 |
| DOI: | 10.1016/j.kint.2015.12.005 |
| Popis: | Peritoneal dialysis (PD) can result in chronic inflammation and progressive peritoneal membrane damage. Alanyl-Glutamine (Ala-Gln), a dipeptide with immunomodulatory effects, improved resistance of mesothelial cells to PD fluids. Recently, interleukin-17 (IL-17) was found to be associated with PD-induced peritoneal damage. Here we studied the capacity of intraperitoneal Ala-Gln administration to protect against peritoneal damage by modulating IL-17 expression in uremic rat and mouse PD exposure models. Supplementation of PD fluid with Ala-Gln resulted in reduced peritoneal thickness, αSMA expression and angiogenesis. Addition of Ala-Gln also attenuated the IL-17 pathway expression induced by PD, reflected by substantial reduction or normalization of peritoneal levels of IL-17, transforming growth factor β, IL-6, and the transcription factor retinoic acid receptor-related orphan receptor gamma T. Moreover, increased levels of IL-17 were associated with PD-induced peritoneal thickening. Conversely, Ala-Gln treatment prevented peritoneal extracellular matrix deposition, an effect seen with IL-17 blockade. Thus, intraperitoneal administration of Ala-Gln, a stable dipeptide commonly used in parenteral nutrition, ameliorates PD-induced peritoneal damage in animal models, in part by modulating IL-17 expression. Hence, Ala-Gln supplementation of dialysate may be a potential strategy to ameliorate peritoneal deterioration during PD. |
| Databáze: | OpenAIRE |
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