Cytoprotection by erythropoietin in hypoxia-ischaemia of the kidney and brain

我们的目标是通过描述保护肾脏和脑细胞免受缺氧引起的压力的复杂机制，来产生重大的研究影响。特别是，我们将确定复合促红细胞生成素(EPO)是否有助于保护细胞免受缺氧后的死亡。EPO是自然存在于人体中的，但其人类重组形式也可用于治疗。。我们已经描述了EPO如何保护肾脏，但还没有人描述它对肾脏细胞分化的作用，或者它对受损肾脏结构和血管支持的影响。促红细胞生成素治疗什么时候可能有效？它能预防慢性肾脏疾病吗？同样，虽然更多的早产儿存活下来，但这是一个关键时期，他们对缺氧高度敏感，由于大脑中关键结构细胞缺乏成熟，他们面临大脑损伤和发育不良的风险。促红细胞生成素在帮助脑细胞成熟以及在这一发育不良时期对血管形成和功能的作用尚不清楚。这两个健康问题都是重大问题，给社会带来了巨大的经济和情感代价。尽管早期证据表明EPO在人类疾病治疗中发挥了有用的作用，但目前的实验和临床数据表明，进一步深入研究机制和细胞通路是改善临床结果的重要基础。我们项目的一个特别优势是，通过比较肾脏和大脑的异同，我们将能够阐明EPO及其类似物的作用机制。

We aim to make a significant research impact by describing the complex mechanisms responsible for protecting kidney and brain cells from stress caused by a lack of oxygen. In particular we will establish whether the compound erythropoietin (Epo), which occurs naturally in the human body but its human recombinant form can also be used as a treatment, may be useful in protecting cells from death following a shortage of oxygen. . We have already described how Epo can protect the kidney, but no one has yet described its action on kidney cell differentiation or its effect on structural and vascular support in the injured kidney. When might Epo treatment be effective? Could it protect against chronic renal disease? Likewise, whilst more very pre-term babies survive, this is a crucial period when they are at heightened sensitivity to lack of oxygen and they are at risk of brain damage and poor development because of lack of maturation of key structural cells in the brain. The role of Epo in aiding brain cell maturation and on blood vessel formation and function in this faulty development period is not known. Both of these health problems are major issues causing huge costs to society both financial and emotional. Despite the early evidence of a useful role for Epo in human disease treatment, current experimental and clinical data demonstrate the importance of further thorough investigation of mechanisms and cellular pathways that will underpin improvements in clinical outcomes. A particular strength of our project is that by comparing similarities and differences in the kidney and brain, we will be able to elucidate the mechanisms of action of Epo and its analogues.