Deviating macrophage activation in glomerulonephritis by SOCS proteins

肾功能衰竭是世界范围内巨大的经济、身体和精神负担，也是发病率和死亡率的重要原因。目前，移植或透析是这种致残疾病的唯一治疗方法，而防止这种疾病的唯一方法是设计出更有效的方法来治疗导致进行性损伤并最终破坏肾脏的肾脏疾病。为此，我们制定了一项研究计划，重点是渗透巨噬细胞的作用，巨噬细胞是所有类型的严重和进行性肾脏疾病的共同特征。许多关于巨噬细胞的工作是基于它们引起组织损伤的能力，然而现在很明显，巨噬细胞也可以促进损伤的解决和促进组织修复。我们的研究旨在抑制巨噬细胞的破坏性，并利用其修复能力，从而创造出治疗炎症性疾病的细胞。我们已经通过抑制特定的巨噬细胞细胞内信号通路来创建一种抗炎治疗性巨噬细胞，在实验模型中下调肾脏炎症，从而证明了这一原理。我们现在希望扩大我们的研究范围，使用更自然的方法将巨噬细胞培养成治疗性细胞，为此，我们将研究细胞因子信号转导抑制物(SOCS)家族的作用，其中两个家族(SOCS1和SOCS3)在巨噬细胞中具有重要作用。我们推测，这些蛋白的表达将对炎症组织中巨噬细胞的特性产生强大的影响，改变它们在巨噬细胞中的表达可能会对抑制肾炎的进展产生影响。如果我们的假设是正确的，这可能为更有效地治疗肾脏疾病和其他类型的炎症性疾病奠定基础。

Renal failure is an enormous financial, physical and emotional burden worldwide and a significant cause of morbidity and mortality. At present transplantation or dialysis is the only treatment for this disabilitating disease and the only way to prevent this is devise much more effective ways to treat kidney diseases that cause progressive injury and eventually destroy the kidney. We have developed a programme of research with this purpose that focuses on the role of infiltrating macrophages, important white blood cells that are a common feature of all types of severe and progressive kidney disease. Much of the work on macrophages is based on their ability to cause tissue injury however it is now apparent that macrophages can also facilitate resolution of injury and promote tissue repair. Our research aims to inhibit the destructive properties and harness the reparative potential of macrophages so to create therapeutic cells for treatment of inflammatory diseases. We have developed proof of this principal by inhibiting specific macrophage intracellular signalling pathways to create an anti-inflammatory therapeutic macrophage that down regulates renal inflammation in experimental models. We now want to expand our research to use more natural methods of developing macrophages to become therapeutic cells and for this purpose we will investigate the role of suppressors of cytokine signalling (SOCS) family of which two (SOCS1 and SOCS3) have an important role in macrophages. We hypothesise that the expression of these proteins will have a powerful effect on the properties macrophages develop in inflamed tissue and changing their expression in macrophages could have a influential effect on inhibiting progression of renal inflammation. If our hypothesis is correct this could form the basis of much more effective treatments for kidney disease as well as other types of inflammatory disorders.