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首页> 外文期刊>Transplantation: Official Journal of the Transplantation Society >Epigenetics in Kidney Transplantation: Current Evidence, Predictions, and Future Research Directions
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Epigenetics in Kidney Transplantation: Current Evidence, Predictions, and Future Research Directions

机译:肾脏移植的表观遗传学:当前证据,预测和未来研究方向

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摘要

Epigenetic modifications are changes to the genome that occur without any alteration in DNA sequence. These changes include cytosine methylation of DNA at cytosine-phosphate diester-guanine dinucleotides, histone modifications, microRNA interactions, and chromatin remodeling complexes. Epigenetic modifications may exert their effect independently or complementary to genetic variants and have the potential to modify gene expression. These modifications are dynamic, potentially heritable, and can be induced by environmental stimuli or drugs. There is emerging evidence that epigenetics play an important role in health and disease. However, the impact of epigenetic modifications on the outcomes of kidney transplantation is currently poorly understood and deserves further exploration. Kidney transplantation is the best treatment option for end-stage renal disease, but allograft loss remains a significant challenge that leads to increased morbidity and return to dialysis. Epigenetic modifications may influence the activation, proliferation, and differentiation of the immune cells, and therefore may have a critical role in the host immune response to the allograft and its outcome. The epigenome of the donor may also impact kidney graft survival, especially those epigenetic modifications associated with early transplant stressors (eg, cold ischemia time) and donor aging. In the present review, we discuss evidence supporting the role of epigenetic modifications in ischemia-reperfusion injury, host immune response to the graft, and graft response to injury as potential new tools for the diagnosis and prediction of graft function, and new therapeutic targets for improving outcomes of kidney transplantation.
机译:表观遗传修饰是指基因组发生的变化,而DNA序列没有任何变化。这些变化包括胞嘧啶-磷酸二酯-鸟嘌呤二核苷酸处DNA的胞嘧啶甲基化,组蛋白修饰,microRNA相互作用和染色质重塑复合物。表观遗传修饰可以独立发挥作用或与遗传变异互补,并具有修饰基因表达的潜力。这些修饰是动态的,可能是遗传的,并且可以由环境刺激或药物诱导。越来越多的证据表明表观遗传学在健康和疾病中起着重要的作用。然而,表观遗传修饰对肾移植结果的影响目前知之甚少,值得进一步探讨。肾脏移植是终末期肾脏疾病的最佳治疗选择,但同种异体移植仍然是一项重大挑战,导致发病率增加并重新回到透析状态。表观遗传修饰可能会影响免疫细胞的激活,增殖和分化,因此可能在宿主对同种异体移植物及其结果的免疫反应中起关键作用。供体的表观基因组也可能影响肾移植物的存活,特别是与早期移植物应激因素(例如冷缺血时间)和供体衰老相关的表观遗传修饰。在本综述中,我们讨论了支持表观遗传修饰在缺血再灌注损伤中的作用,宿主对移植物的免疫反应以及对损伤的移植物反应的潜在证据,这些方法可作为诊断和预测移植物功能的潜在新工具,以及新的治疗靶点改善肾脏移植的结果。

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