TY - JOUR
T1 - Altered phosphorylation of cytoskeleton proteins in peripheral blood mononuclear cells characterizes chronic antibody-mediated rejection in kidney transplantation
AU - Rocchetti, Maria Teresa
AU - Rascio, Federica
AU - Castellano, Giuseppe
AU - Fiorentino, Marco
AU - Netti, Giuseppe Stefano
AU - Spadaccino, Federica
AU - Ranieri, Elena
AU - Gallone, Anna
AU - Gesualdo, Loreto
AU - Stallone, Giovanni
AU - Pontrelli, Paola
AU - Grandaliano, Giuseppe
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - Actin-related protein 2
KW - Chronic antibody-mediated rejection
KW - F-actin
KW - Kidney transplantation
KW - Phosphoproteome
KW - Actin-related protein 2
KW - Chronic antibody-mediated rejection
KW - F-actin
KW - Kidney transplantation
KW - Phosphoproteome
UR - http://hdl.handle.net/10807/167625
U2 - 10.3390/ijms21186509
DO - 10.3390/ijms21186509
M3 - Article
SN - 1661-6596
VL - 21
SP - 1
EP - 12
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
ER -