Altered phosphorylation of cytoskeleton proteins in peripheral blood mononuclear cells characterizes chronic antibody-mediated rejection in kidney transplantation

Maria Teresa Rocchetti, Federica Rascio, Giuseppe Castellano, Marco Fiorentino, Giuseppe Stefano Netti, Federica Spadaccino, Elena Ranieri, Anna Gallone, Loreto Gesualdo, Giovanni Stallone, Paola Pontrelli, Giuseppe Grandaliano

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number6509
Pages (from-to)1-12
Number of pages12
JournalInternational Journal of Molecular Sciences
Volume21
Issue number18
DOIs
Publication statusPublished - Sep 2 2020
Externally publishedYes

Keywords

  • Actin-related protein 2
  • Chronic antibody-mediated rejection
  • F-actin
  • Kidney transplantation
  • Phosphoproteome

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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