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Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients
INTRODUCTION: The complete systemic deregulated biological network in patients on peritoneal dialysis (PD) is still only partially defined. High-throughput/omics techniques may offer the possibility to analyze the main biological fingerprints associated with this clinical condition. METHODS: We appl...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496084/ https://www.ncbi.nlm.nih.gov/pubmed/37705917 http://dx.doi.org/10.1016/j.ekir.2023.06.017 |
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author | Granata, Simona Bruschi, Maurizio Verlato, Alberto Pontrelli, Paola Gesualdo, Loreto Stallone, Giovanni Zaza, Gianluigi |
author_facet | Granata, Simona Bruschi, Maurizio Verlato, Alberto Pontrelli, Paola Gesualdo, Loreto Stallone, Giovanni Zaza, Gianluigi |
author_sort | Granata, Simona |
collection | PubMed |
description | INTRODUCTION: The complete systemic deregulated biological network in patients on peritoneal dialysis (PD) is still only partially defined. High-throughput/omics techniques may offer the possibility to analyze the main biological fingerprints associated with this clinical condition. METHODS: We applied an innovative bioinformatic analysis of gene expression microarray data (mainly based on support vector machine (SVM) learning) to compare the transcriptomic profile of peripheral blood mononuclear cells (PBMCs) of healthy subjects (HS), chronic kidney disease (CKD) patients, and patients on PD divided into a microarray group (5 HS, 9 CKD, and 10 PD) and a validation group (10 HS, 15 CKD, and 15 PD). Classical well-standardized biomolecular approaches (western blotting and flow cytometry) were used to validate the transcriptomic results. RESULTS: Bioinformatics revealed a distinctive PBMC transcriptomic profiling for PD versus CKD and HS (n = 419 genes). Transcripts encoding for key elements of the autophagic pathway were significantly upregulated in PD, and the autophagy related 5 (ATG5) reached the top level of discrimination [−Log10 P-value = 11.3, variable importance in projection (VIP) score = 4.8, SVM rank:1]. Protein levels of ATG5 and microtubule associated protein 1 light chain 3 beta (LC3B), an important constituent of the autophagosome, validated microarray results. In addition, the incubation of PBMCs of HS with serum of patients on PD upregulated both proteins. Autophagy in PBMCs from patients on PD was attenuated by N-acetyl-cysteine or Resatorvid treatment. CONCLUSIONS: Our data demonstrated, for the first time, that the autophagy pathway is activated in immune-cells of patients on PD, and this may represent a novel therapeutic target. |
format | Online Article Text |
id | pubmed-10496084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-104960842023-09-13 Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients Granata, Simona Bruschi, Maurizio Verlato, Alberto Pontrelli, Paola Gesualdo, Loreto Stallone, Giovanni Zaza, Gianluigi Kidney Int Rep Translational Research INTRODUCTION: The complete systemic deregulated biological network in patients on peritoneal dialysis (PD) is still only partially defined. High-throughput/omics techniques may offer the possibility to analyze the main biological fingerprints associated with this clinical condition. METHODS: We applied an innovative bioinformatic analysis of gene expression microarray data (mainly based on support vector machine (SVM) learning) to compare the transcriptomic profile of peripheral blood mononuclear cells (PBMCs) of healthy subjects (HS), chronic kidney disease (CKD) patients, and patients on PD divided into a microarray group (5 HS, 9 CKD, and 10 PD) and a validation group (10 HS, 15 CKD, and 15 PD). Classical well-standardized biomolecular approaches (western blotting and flow cytometry) were used to validate the transcriptomic results. RESULTS: Bioinformatics revealed a distinctive PBMC transcriptomic profiling for PD versus CKD and HS (n = 419 genes). Transcripts encoding for key elements of the autophagic pathway were significantly upregulated in PD, and the autophagy related 5 (ATG5) reached the top level of discrimination [−Log10 P-value = 11.3, variable importance in projection (VIP) score = 4.8, SVM rank:1]. Protein levels of ATG5 and microtubule associated protein 1 light chain 3 beta (LC3B), an important constituent of the autophagosome, validated microarray results. In addition, the incubation of PBMCs of HS with serum of patients on PD upregulated both proteins. Autophagy in PBMCs from patients on PD was attenuated by N-acetyl-cysteine or Resatorvid treatment. CONCLUSIONS: Our data demonstrated, for the first time, that the autophagy pathway is activated in immune-cells of patients on PD, and this may represent a novel therapeutic target. Elsevier 2023-06-26 /pmc/articles/PMC10496084/ /pubmed/37705917 http://dx.doi.org/10.1016/j.ekir.2023.06.017 Text en © 2023 International Society of Nephrology. Published by Elsevier Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Translational Research Granata, Simona Bruschi, Maurizio Verlato, Alberto Pontrelli, Paola Gesualdo, Loreto Stallone, Giovanni Zaza, Gianluigi Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients |
title | Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients |
title_full | Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients |
title_fullStr | Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients |
title_full_unstemmed | Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients |
title_short | Autophagy Activation in Peripheral Blood Mononuclear Cells of Peritoneal Dialysis Patients |
title_sort | autophagy activation in peripheral blood mononuclear cells of peritoneal dialysis patients |
topic | Translational Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10496084/ https://www.ncbi.nlm.nih.gov/pubmed/37705917 http://dx.doi.org/10.1016/j.ekir.2023.06.017 |
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