Dissecting recipient from donor contribution in experimental kidney transplantation: focus on endothelial proliferation and inflammation.
Dissecting recipient from donor contribution in experimental kidney transplantation: focus on endothelial proliferation and inflammation.
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DOI：
10.1242/dmm.035030
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发表时间：
2018-07-17
影响因子：
4.3
通讯作者：
Verhaar MC
中科院分区：
文献类型：
--
作者：
Papazova DA;Krebber MM;Oosterhuis NR;Gremmels H;van Zuilen AD;Joles JA;Verhaar MC
肾移植(TX)被认为是治疗终末期肾病(ESKD)患者的唯一确定的治疗方法。ESKD的流行越来越普遍，因此有必要采用不理想的供者的肾脏进行移植。然而，仍然缺乏关于次优肾移植的基础和纵向研究。具体地说，需要准确的移植前肾功能和损伤的预测指标来预测移植后的结果。在目前的研究中，我们结合慢性肾脏疾病(CKD)的大鼠模型和肾脏TX来分析健康和CKD肾移植对健康和CKD受体的影响。我们的研究表明，移植后6周的肾功能完全取决于供者移植的质量。通过对增强型绿色荧光蛋白阳性(EGFP+)受者的细胞追踪，我们进一步表明，供体肾脏内的大多数炎症细胞来自供体。相反，氧化损伤和肾外血管损伤则由受者决定。移植后和移植前的评估显示，在健康的CKD移植物中，肾小球和管周毛细血管疏松增加，但在CKD环境中，CKD移植物没有增加。所有组的肾小球内皮细胞增殖情况相似，无论移植物或受体状态如何，都会出现EGFP+受体衍生细胞的涌入。然而，肾小球和肾小管周围毛细血管疏松、炎症严重程度和巨噬细胞亚型数据在TX后由更复杂的效应决定，需要进一步研究。我们的实验模型可以帮助进一步区分移植物与受体环境的影响，导致新的策略来提高次优TX肾的移植物存活率。本文对这篇论文的第一作者进行了相关的第一人称采访。摘要：利用实验性肾移植，我们解剖了供体移植物对受体环境的影响，重点放在内皮和炎症方面。这些结果可以指导改善次优移植后移植物存活率的策略。
Kidney transplantation (Tx) is considered the only definite treatment for end-stage kidney disease (ESKD) patients. The increasing prevalence of ESKD has necessitated the introduction of transplantation with kidneys from suboptimal donors. There is, however, still a lack of fundamental and longitudinal research on suboptimal kidney transplants. Specifically, there is a demand for accurate pre-Tx predictors of donor kidney function and injury to predict post-Tx outcome. In the present study, we combine rat models of chronic kidney disease (CKD) and renal Tx to dissect the effects of healthy and CKD renal grafts on healthy and CKD recipients. We show that renal function at 6 weeks post-Tx is exclusively determined by donor graft quality. Using cell tracking within enhanced green fluorescent protein-positive (eGFP+) recipients, we furthermore show that most inflammatory cells within the donor kidney originate from the donor. Oxidative and vascular extra-renal damage were, in contrast, determined by the recipient. Post- versus pre-Tx evaluation of grafts showed an increase in glomerular and peritubular capillary rarefaction in healthy but not CKD grafts within a CKD environment. Proliferation of glomerular endothelium was similar in all groups, and influx of eGFP+ recipient-derived cells occurred irrespective of graft or recipient status. Glomerular and peritubular capillary rarefaction, severity of inflammation and macrophage subtype data post-Tx were, however, determined by more complicated effects, warranting further study. Our experimental model could help to further distinguish graft from recipient environment effects, leading to new strategies to improve graft survival of suboptimal Tx kidneys. This article has an associated First Person interview with the first author of the paper. Summary: Using experimental kidney transplantation, we dissected donor graft from recipient environment effects, focusing on the endothelium and inflammation. These results can direct strategies to improve graft survival after suboptimal transplantation.
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影响因子：
3.7
作者：
Bergler T;Jung B;Bourier F;Kühne L;Banas MC;Rümmele P;Wurm S;Banas B
通讯作者：
Banas B
DOI：
10.1152/ajpregu.00727.2009
发表时间：
2010-03-01
影响因子：
2.8
作者：
Bongartz, L. G.;Braam, B.;Joles, J. A.
通讯作者：
Joles, J. A.
DOI：
10.1152/ajprenal.00009.2002
发表时间：
2003-04-01
影响因子：
4.2
作者：
Attia, DM;Goldschmeding, R;Joles, JA
通讯作者：
Joles, JA
影响因子：
3.2
作者：
Kwon, Osun;Miller, Shane;Uemura, Tadahiro
通讯作者：
Uemura, Tadahiro
DOI：
10.1152/ajprenal.00221.2010
发表时间：
2010-11-01
影响因子：
4.2
作者：
Kelley, Rusty;Werdin, Eric S.;Presnell, Sharon C.
通讯作者：
Presnell, Sharon C.