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Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation
Chronic antibody-mediated rejection (CAMR) is the major cause of kidney transplant failure. The molecular mechanisms underlying this event are still poorly defined and this lack of knowledge deeply influences the potential therapeutic strategies. The aim of our study was to analyze the phosphoproteo...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556000/ https://www.ncbi.nlm.nih.gov/pubmed/32899575 http://dx.doi.org/10.3390/ijms21186509 |
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author | Rocchetti, Maria Teresa Rascio, Federica Castellano, Giuseppe Fiorentino, Marco Netti, Giuseppe Stefano Spadaccino, Federica Ranieri, Elena Gallone, Anna Gesualdo, Loreto Stallone, Giovanni Pontrelli, Paola Grandaliano, Giuseppe |
author_facet | Rocchetti, Maria Teresa Rascio, Federica Castellano, Giuseppe Fiorentino, Marco Netti, Giuseppe Stefano Spadaccino, Federica Ranieri, Elena Gallone, Anna Gesualdo, Loreto Stallone, Giovanni Pontrelli, Paola Grandaliano, Giuseppe |
author_sort | Rocchetti, Maria Teresa |
collection | PubMed |
description | Chronic antibody-mediated rejection (CAMR) is the major cause of kidney transplant failure. The molecular mechanisms underlying this event are still poorly defined and this lack of knowledge deeply influences the potential therapeutic strategies. The aim of our study was to analyze the phosphoproteome of peripheral blood mononuclear cells (PBMCs), to identify cellular signaling networks differentially activated in CAMR. Phosphoproteins isolated from PBMCs of biopsy proven CAMR, kidney transplant recipients with normal graft function and histology and healthy immunocompetent individuals, have been investigated by proteomic analysis. Phosphoproteomic results were confirmed by Western blot and PBMCs’ confocal microscopy analyses. Overall, 38 PBMCs samples were analyzed. A differential analysis of PBMCs’ phosphoproteomes revealed an increase of lactotransferrin, actin-related protein 2 (ARPC2) and calgranulin-B in antibody-mediated rejection patients, compared to controls. Increased expression of phosphorylated ARPC2 and its correlation to F-actin filaments were confirmed in CAMR patients. Our results are the first evidence of altered cytoskeleton organization in circulating immune cells of CAMR patients. The increased expression of phosphorylated ARPC2 found in the PBMCs of our patients, and its association with derangement of F-actin filaments, might suggest that proteins regulating actin dynamics in immune cells could be involved in the mechanism of CAMR of kidney grafts. |
format | Online Article Text |
id | pubmed-7556000 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75560002020-10-19 Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation Rocchetti, Maria Teresa Rascio, Federica Castellano, Giuseppe Fiorentino, Marco Netti, Giuseppe Stefano Spadaccino, Federica Ranieri, Elena Gallone, Anna Gesualdo, Loreto Stallone, Giovanni Pontrelli, Paola Grandaliano, Giuseppe Int J Mol Sci Article Chronic antibody-mediated rejection (CAMR) is the major cause of kidney transplant failure. The molecular mechanisms underlying this event are still poorly defined and this lack of knowledge deeply influences the potential therapeutic strategies. The aim of our study was to analyze the phosphoproteome of peripheral blood mononuclear cells (PBMCs), to identify cellular signaling networks differentially activated in CAMR. Phosphoproteins isolated from PBMCs of biopsy proven CAMR, kidney transplant recipients with normal graft function and histology and healthy immunocompetent individuals, have been investigated by proteomic analysis. Phosphoproteomic results were confirmed by Western blot and PBMCs’ confocal microscopy analyses. Overall, 38 PBMCs samples were analyzed. A differential analysis of PBMCs’ phosphoproteomes revealed an increase of lactotransferrin, actin-related protein 2 (ARPC2) and calgranulin-B in antibody-mediated rejection patients, compared to controls. Increased expression of phosphorylated ARPC2 and its correlation to F-actin filaments were confirmed in CAMR patients. Our results are the first evidence of altered cytoskeleton organization in circulating immune cells of CAMR patients. The increased expression of phosphorylated ARPC2 found in the PBMCs of our patients, and its association with derangement of F-actin filaments, might suggest that proteins regulating actin dynamics in immune cells could be involved in the mechanism of CAMR of kidney grafts. MDPI 2020-09-05 /pmc/articles/PMC7556000/ /pubmed/32899575 http://dx.doi.org/10.3390/ijms21186509 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rocchetti, Maria Teresa Rascio, Federica Castellano, Giuseppe Fiorentino, Marco Netti, Giuseppe Stefano Spadaccino, Federica Ranieri, Elena Gallone, Anna Gesualdo, Loreto Stallone, Giovanni Pontrelli, Paola Grandaliano, Giuseppe Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation |
title | Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation |
title_full | Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation |
title_fullStr | Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation |
title_full_unstemmed | Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation |
title_short | Altered Phosphorylation of Cytoskeleton Proteins in Peripheral Blood Mononuclear Cells Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation |
title_sort | altered phosphorylation of cytoskeleton proteins in peripheral blood mononuclear cells characterizes chronic antibody-mediated rejection in kidney transplantation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556000/ https://www.ncbi.nlm.nih.gov/pubmed/32899575 http://dx.doi.org/10.3390/ijms21186509 |
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