Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model

  • Darragh P. O'Brien (Ophavsperson)
  • Adam M. Thorne (Ophavsperson)
  • Honglei Huang (Ophavsperson)
  • Elisa Pappalardo (Ophavsperson)
  • Xuan Yao (Ophavsperson)
  • Peter Søndergaard Thyrrestrup (Ophavsperson)
  • Kristian Ravlo (Ophavsperson)
  • Niels Secher (Ophavsperson)
  • Rikke Norregaard (Ophavsperson)
  • Rutger J. Ploeg (Ophavsperson)
  • Bente Jespersen (Ophavsperson)
  • Benedikt M. Kessler (Ophavsperson)

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Abstract Background Remote Ischemic Conditioning (RIC) has been proposed as a therapeutic intervention to circumvent the ischemia/reperfusion injury (IRI) that is inherent to organ transplantation. Using a porcine kidney transplant model, we aimed to decipher the subclinical molecular effects of a RIC regime, compared to non-RIC controls. Methods Kidney pairs (n = 8 + 8) were extracted from brain dead donor pigs and transplanted in juvenile recipient pigs following a period of cold ischemia. One of the two kidney recipients in each pair was subjected to RIC prior to kidney graft reperfusion, while the other served as non-RIC control. We designed an integrative Omics strategy combining transcriptomics, proteomics, and phosphoproteomics to deduce molecular signatures in kidney tissue that could be attributed to RIC. Results In kidney grafts taken out 10 h after transplantation we detected minimal molecular perturbations following RIC compared to non-RIC at the transcriptome level, which was mirrored at the proteome level. In particular, we noted that RIC resulted in suppression of tissue inflammatory profiles. Furthermore, an accumulation of muscle extracellular matrix assembly proteins in kidney tissues was detected at the protein level, which may be in response to muscle tissue damage and/or fibrosis. However, the majority of these protein changes did not reach significance (p
Dato for tilgængelighed2022
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