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

我们的目标是通过描述负责保护肾脏和脑细胞免受缺氧引起的压力的复杂机制，产生重大的研究影响。特别是，我们将确定是否复合促红细胞生成素（Epo）可能有助于保护细胞免于缺氧后的死亡，它在人体中自然存在，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细胞分化的作用或它对损伤肾脏的结构和血管支持的影响。什么时候促生成素治疗可能有效？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，但这是他们对缺氧高度敏感的关键时期，由于大脑中关键结构细胞缺乏成熟，他们面临脑损伤和发育不良的风险。Epo在帮助脑细胞成熟和在这一缺陷发育时期的血管形成和功能中的作用尚不清楚。这两种健康问题都是给社会造成巨大经济和情感成本的主要问题。尽管早期证据表明Epo在人类疾病治疗中的有用作用，但目前的实验和临床数据表明，进一步深入研究其机制和细胞途径的重要性，这将巩固临床结果的改善。我们项目的一个特别优势是，通过比较肾脏和大脑的异同，我们将能够阐明促红细胞生成素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.