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

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 regim...

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Autores principales: O’Brien, Darragh P., Thorne, Adam M., Huang, Honglei, Pappalardo, Elisa, Yao, Xuan, Thyrrestrup, Peter Søndergaard, Ravlo, Kristian, Secher, Niels, Norregaard, Rikke, Ploeg, Rutger J., Jespersen, Bente, Kessler, Benedikt M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903695/
https://www.ncbi.nlm.nih.gov/pubmed/35164671
http://dx.doi.org/10.1186/s12014-022-09343-3
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author O’Brien, Darragh P.
Thorne, Adam M.
Huang, Honglei
Pappalardo, Elisa
Yao, Xuan
Thyrrestrup, Peter Søndergaard
Ravlo, Kristian
Secher, Niels
Norregaard, Rikke
Ploeg, Rutger J.
Jespersen, Bente
Kessler, Benedikt M.
author_facet O’Brien, Darragh P.
Thorne, Adam M.
Huang, Honglei
Pappalardo, Elisa
Yao, Xuan
Thyrrestrup, Peter Søndergaard
Ravlo, Kristian
Secher, Niels
Norregaard, Rikke
Ploeg, Rutger J.
Jespersen, Bente
Kessler, Benedikt M.
author_sort O’Brien, Darragh P.
collection PubMed
description 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 < 0.05). CONCLUSIONS: Our data identifies subtle molecular phenotypes in porcine kidneys following RIC, and this knowledge could potentially aid optimization of remote ischemic conditioning protocols in renal transplantation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-022-09343-3.
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spelling pubmed-89036952022-03-18 Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model O’Brien, Darragh P. Thorne, Adam M. Huang, Honglei Pappalardo, Elisa Yao, Xuan Thyrrestrup, Peter Søndergaard Ravlo, Kristian Secher, Niels Norregaard, Rikke Ploeg, Rutger J. Jespersen, Bente Kessler, Benedikt M. Clin Proteomics Research 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 < 0.05). CONCLUSIONS: Our data identifies subtle molecular phenotypes in porcine kidneys following RIC, and this knowledge could potentially aid optimization of remote ischemic conditioning protocols in renal transplantation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12014-022-09343-3. BioMed Central 2022-02-14 /pmc/articles/PMC8903695/ /pubmed/35164671 http://dx.doi.org/10.1186/s12014-022-09343-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
O’Brien, Darragh P.
Thorne, Adam M.
Huang, Honglei
Pappalardo, Elisa
Yao, Xuan
Thyrrestrup, Peter Søndergaard
Ravlo, Kristian
Secher, Niels
Norregaard, Rikke
Ploeg, Rutger J.
Jespersen, Bente
Kessler, Benedikt M.
Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model
title Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model
title_full Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model
title_fullStr Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model
title_full_unstemmed Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model
title_short Integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model
title_sort integrative omics reveals subtle molecular perturbations following ischemic conditioning in a porcine kidney transplant model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8903695/
https://www.ncbi.nlm.nih.gov/pubmed/35164671
http://dx.doi.org/10.1186/s12014-022-09343-3
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