Expression and significance of the P2X7 purinoceptor in Diabetic Nephropathy

糖尿病肾病(糖尿病肾病)是糖尿病的一种严重且日益普遍的并发症；其特征是肾小球(滤过单位)逐渐形成疤痕。尽管糖尿病的治疗有所改善，但许多患者的肾功能继续下降，最终需要透析或移植。目前的治疗方法减缓了一部分患者的进展，但并不能阻止这种情况，迫切需要新的治疗形式。一种被称为P2X7受体(P2X7R)的ATP受体可在肾脏细胞表面表达，已被认为与肾脏损伤有关，包括糖尿病。这项建议的目的是调查该受体是否与糖尿病肾病有关。概述的研究涉及使用人类肾脏活检切片和尿样的组合方法，以及不表达P2X7R的小鼠的糖尿病模型(如果P2X7R在糖尿病中很重要，缺乏这种受体应该会降低疾病的严重性)，以及体外肾细胞培养，以确定P2X7R可能导致疾病的机制。证明P2X7R在糖尿病肾病中的作用可能导致开发一种新的治疗这种顽固性疾病的方法。

Diabetic kidney disease (diabetic nephropathy) is a serious and increasingly prevalent complication of diabetes; it is characterised by progressive scarring of the kidney glomeruli (the filtration units). Despite improvements in the treatment of diabetes, renal function in many patients continues to decline, eventually requiring dialysis or transplantation. Current treatments slow progression in a proportion of patients but do not prevent this, and there is a pressing need for new forms of treatment. An ATP receptor known as the P2X7 receptor (P2X7R) that can be expressed on the surface of cells in the kidney has been linked to kidney injury, including in diabetes. The aim of this proposal is to investigate whether this receptor is involved in diabetic nephropathy. The studies outlined involve a combined approach using human kidney biopsy sections and urine samples, and a model of diabetes in mice that do not express P2X7R (if P2X7R is important in diabetes, lack of this receptor should reduce disease severity), as well as in vitro kidney cell cultures, to define the mechanisms whereby P2X7R may cause disease. Demonstrating a role for P2X7R in diabetic nephropathy could lead to development of a novel therapy for this intractable disease.