Kidney Week

Abstract: FR-PO853

Extracellular Vesicles (EVs) Induce Tubular Epithelial Cells (TEC) Inflammaging in Antibody-Mediated Rejection (AMR)

Session Information

• Transplantation: Basic
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 1801 Transplantation: Basic

Authors

• Divella, Chiara, University of Bari, BARI, Italy

Chiara Divella,

• Stasi, Alessandra, University of Bari, BARI, Italy

Alessandra Stasi,

• Franzin, Rossana, University of Bari, BARI, Italy

Rossana Franzin,

• Sallustio, Fabio, University of Bari, BARI, Italy

Fabio Sallustio,

• Curci, Claudia, University of Bari, BARI, Italy

Claudia Curci,

• Merlotti, Guido, University of Piemonte Orientale, Novara, Italy

Guido Merlotti,

• Quaglia, Marco, Università del Piemonte Orientale, Torino, Italy

Marco Quaglia,

• Gesualdo, Loreto, University of Bari, BARI, Italy

Loreto Gesualdo,

• Cantaluppi, Vincenzo, University of Piemonte Orientale (UPO), Novara, Italy

Vincenzo Cantaluppi,

• Castellano, Giuseppe, University of Bari, BARI, Italy

Giuseppe Castellano,

Background

Recent data suggest a strong correlation between chronic kidney disease development and activation of accelerated senescence processes known as “inflammaging” in tubular epithelial cells (TEC). However, the role of TEC inflammaging and its mediators in kidney transplantation remains incompletely understood.

Methods

Renal biopsies of 10 transplanted patients with Acute and Chronic AMR were collected. Serum samples (5% for 24h) and EVs isolated from the same patients (5E⁺⁴EVs/cells target for 24h) were incubated with primary culture of TEC (3th passage); p21 and p53 gene levels were measured by qPCR to assess TEC senescence. IHC staining for markers of inflammaging (p16^INK4a and Klotho) were performed on paraffin tissue of the same patients.

Results

Pre-implantation biopsies did not showed signs of TEC Inflammaging. TEC from patients with Chronic AMR expressed significant levels of p16^INK4a indicating occurrence of senescence phenotype, compared with Acute AMR (p<0.05). In vitro, the exposure of TEC to serum of Acute and Chronic AMR patients induced senescence by up-regulating of p21 and p53 gene levels, compared to basal condition (p<0.05). Interestingly, EVs isolated from the AMR patients induced senescence in vitro promoting a significant increase in p21, p53 and cyp1b1 gene level, and a down-regulation of klotho gene (p<0.05).

Conclusion

Our data demonstrated that TEC inflammaging induced by EVs might represent a new pathogenetic mechanism involved in acute and chronic AMR and could be identified as a potential new therapeutic target to counteract accelerated aging in kidney transplantation.