The ClC-5 Cl- channel, a key regulatory role in albumin uptake by the proximal tubule

ClC-5 Cl-通道，在近端小管摄取白蛋白中起关键调节作用

• 批准号: nhmrc : 351411
• 负责人: Prof Carol Pollock
• 金额: $ 34.04万
• 依托单位: The University of Queensland
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2005
• 资助国家: 澳大利亚
• 起止时间: 2005-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/clc-5-cl-proximal-tubule/96409
• 关键词: ClC; Cl; channel; key; regulatory

The clinical association between protein loss in the urine and retention of salt, resulting in high blood pressure and progressive decline in kidney function, is well known. Under normal conditions, the kidneys filter 180 litres of water and reabsorb 1.7 kg of salt per day, a function which is principally performed by the kidney tubules in the kidney. Similarly the kidney tubule cells reabsorb and break down up to 3 grams of albumin per day. In the past, it has been considered that excessive protein loss in the urine is primarily due to problems in the filtering units of the kidneys, rather than due to abnormalities in the reabsorption of protein in the kidney tubules. However, we consider that common abnormalities in the processes within the kidney tubules that regulate both the reabsorption of salt and the excretion of acid may result in concomitant high blood pressure and increased protein loss in the kidney. Thus the overall aim of the project is to investigate the mechanisms by which the complex responsible for protein uptake determines the interrelationship between protein reabsorption and catabolism and the ion transporting proteins in the membrane of the proximal tubule. This project will comprehensively characterise the mechanisms of protein uptake in kidney tubule cells. The exact nature of the interaction of the proteins involved in performing the salt reabsorption and ensuring correct catabolism of protein uptake with the actual protein uptake mechanism will be determined. As persistent proteinuria is the most important predictor of tubulointerstitial pathology and progressive decline in renal function in almost all renal disease, the understanding of the precise mechanism by which this occurs is essential in the design of renoprotective therapies.

众所周知，尿蛋白丢失与盐滞留之间的临床联系，会导致高血压和肾脏功能的进行性下降。在正常情况下，肾脏每天过滤180升水并重新吸收1.7公斤盐，这一功能主要由肾脏中的肾小管执行。同样，肾小管细胞每天重吸收和分解多达3克白蛋白。过去，人们认为尿中蛋白质的过量丢失主要是由于肾脏过滤单元的问题，而不是由于肾小管对蛋白质的重新吸收的异常。然而，我们认为，肾小管内调节盐的重吸收和酸的排泄的过程中常见的异常可能会导致伴随的高血压和肾脏蛋白丢失的增加。因此，该项目的总体目标是研究负责蛋白质摄取的复合体决定蛋白质重吸收和分解代谢与近端小管膜离子转运蛋白质之间的相互关系的机制。该项目将全面描述肾小管细胞摄取蛋白质的机制。进行盐重吸收并确保蛋白质吸收的正确分解代谢与实际蛋白质吸收机制的蛋白质相互作用的确切性质将被确定。在几乎所有的肾脏疾病中，持续性蛋白尿是肾小管间质病变和肾功能进行性衰退的最重要的预测指标，因此对其发生的确切机制的了解在肾保护治疗的设计中是至关重要的。