Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark.
Cell Tissue Res. 2021 Aug;385(2):489-500. doi: 10.1007/s00441-021-03433-8. Epub 2021 Apr 17.
Proteases play a central role in regulating renal pathophysiology and are increasingly evaluated as actionable drug targets. Here, we review the role of proteolytic systems in inflammatory kidney disease. Inflammatory kidney diseases are associated with broad dysregulations of extracellular and intracellular proteolysis. As an example of a proteolytic system, the complement system plays a significant role in glomerular inflammatory kidney disease and is currently under clinical investigation. Based on two glomerular kidney diseases, lupus nephritis, and membranous nephropathy, we portrait two proteolytic pathomechanisms and the role of the complement system. We discuss how profiling proteolytic activity in patient samples could be used to stratify patients for more targeted interventions in inflammatory kidney diseases. We also describe novel comprehensive, quantitative tools to investigate the entirety of proteolytic processes in a tissue sample. Emphasis is placed on mass spectrometric approaches that enable the comprehensive analysis of the complement system, as well as protease activities and regulation in general.
蛋白酶在调节肾脏生理病理中起着核心作用，并且越来越多地被评估为可作用的药物靶点。在这里，我们综述了蛋白水解系统在炎症性肾病中的作用。炎症性肾病与细胞外和细胞内蛋白水解的广泛失调有关。作为蛋白水解系统的一个例子，补体系统在肾小球炎症性肾病中起着重要作用，目前正在进行临床研究。基于两种肾小球肾脏疾病，狼疮肾炎和膜性肾病，我们描述了两种蛋白水解发病机制和补体系统的作用。我们讨论了如何在患者样本中分析蛋白水解活性，以便对炎症性肾病患者进行更有针对性的干预。我们还描述了新的全面、定量的工具，以研究组织样本中蛋白水解过程的整体情况。重点是能够全面分析补体系统以及一般蛋白酶活性和调节的质谱方法。
