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
Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Nuffield Department of Surgical Sciences and Oxford Biomedical Research Centre, University of Oxford, Oxford, UK.
Clin Proteomics. 2022 Feb 14;19(1):6. doi: 10.1186/s12014-022-09343-3.
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.
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.
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).
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.
远程缺血预处理（RIC）已被提议作为一种治疗干预措施，以规避器官移植中固有的缺血/再灌注损伤（IRI）。我们使用猪肾移植模型，旨在解读RIC方案与非RIC对照相比的亚临床分子效应。
从脑死亡供体猪中提取肾对（n = 8 + 8），并在经历一段时间的冷缺血后移植到幼年受体猪中。每对中的两个肾受体之一在肾移植再灌注前接受RIC，而另一个作为非RIC对照。我们设计了一种综合组学策略，结合转录组学、蛋白质组学和磷酸蛋白质组学，以推断肾组织中可归因于RIC的分子特征。
在移植后10小时取出的肾移植物中，与非RIC相比，我们在转录组水平检测到RIC后最小的分子扰动，这在蛋白质组水平也得到了反映。特别是，我们注意到RIC导致组织炎症特征受到抑制。此外，在蛋白质水平检测到肾组织中肌肉细胞外基质组装蛋白的积累，这可能是对肌肉组织损伤和/或纤维化的反应。然而，这些蛋白质变化大多未达到显著水平（p < 0.05）。
我们的数据确定了RIC后猪肾中的细微分子表型，这一知识可能有助于优化肾移植中的远程缺血预处理方案。
