Time of Occurrence of Kidney Acute Antibody-Mediated Allograft Rejection/Acute Cellular Rejection and Cell Senescence: Implications for Function Outcome

Arvizu-Hernández, Mauricio; Morales‐Buenrostro, Luis E.; Vilatobá-Chapa, Mario; Mancilla-Urrea, Eduardo; Uribe‐Uribe, Norma; Avila-Casado, M. Carmen; Leo, Claudia de; Arvizu, Adriana; González, José Luis González; Torres, J. Antonio; Gabilondo, Bernardo; Correa‐Rotter, Ricardo; Alberú, Josefina

doi:10.1016/j.transproceed.2010.04.068

Cited by 4 publications

(2 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Effectively, p16Ink4a level has been associated with senescence‐related renal disease 9,44–46 . Our results are in line with previous findings showing higher level in late (>3 months) episodes compared with early episodes 47 . In accordance, compared with AAMR‐EV, EV from CAMR patients were characterized by a stronger capacity to induce senescence.…”

Section: Discussionsupporting

confidence: 91%

“…9,[44][45][46] Our results are in line with previous findings showing higher level in late (>3 months) episodes compared with early episodes. 47 In accordance, compared with AAMR-EV, EV from CAMR patients were characterized by a stronger capacity to induce senescence. That results are in agreement with findings from Zhang Hao et al 42 that detected gp130 mRNA, a central receptor of IL6, a SASP mediator, 48,49 in circulating EV from AMR patients; furthermore, activation of IL-6 amplifier was recently assessed in urinary exosomes of CAMR patients.…”

Section: Discussionmentioning

confidence: 82%

See 1 more Smart Citation

Extracellular vesicles derived from patients with antibody-mediated rejection induce tubular senescence and endothelial to mesenchymal transition in renal cells

Franzin

Stasi

Sallustio

et al. 2022

American Journal of Transplantation

View full text Add to dashboard Cite

Extracellular vesicles (EV) are emerging mediators in several diseases. However, their role in the pathophysiology of antibody‐mediated allograft rejection (AMR) has been poorly investigated. Here, we investigated the role of EV isolated from AMR patients in inducing tubular senescence and endothelial to mesenchymal transition (EndMT) and analyzed their miRNA expression profile. By multiplex bead flow cytometry, we characterized the immunophenotype of plasma AMR‐derived EV and found a prevalent platelet and endothelial cell origin. In vitro, AMR‐derived EV induced tubular senescence by upregulating SA‐β Gal and CDKN1A mRNA. Furthermore, AMR‐derived EV induced EndMT. The occurrence of tubular senescence and EndMT was confirmed by analysis of renal biopsies from the same AMR patients. Moreover, AMR‐derived EV induced C3 gene upregulation and CFH downregulation in tubular epithelial cells, with C4d deposition on endothelial cells. Interestingly, RNase‐mediated digestion of EV cargo completely abrogated tubular senescence and EndMT. By microarray analysis, miR‐604, miR‐515‐3p, miR‐let‐7d‐5p, and miR‐590‐3p were significantly upregulated in EV from AMR group compared with transplant controls, whereas miR‐24‐3p and miR‐29a‐3p were downregulated. Therefore, EV‐associated miRNA could act as active player in AMR pathogenesis, unraveling potential mechanisms of accelerated graft senescence, complement activation and early fibrosis that might lead to new therapeutic intervention.

show abstract

Section: Discussionsupporting

confidence: 91%