Urine MMP7 as a kidney injury biomarker

NDT Plus Pub Date : 2023-09-14 DOI:10.1093/ckj/sfad233
Alejandro Avello, Juan Guerrero-Mauvecin, Ana Belen Sanz
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Abstract

ABSTRACT Matrix metalloproteinase 7 (MMP-7) is a secreted endopeptidase involved in the degradation of extracellular matrix components and the activation of cytokines and growth factors. The regulation of MMP-7 can be transcriptionally regulated by AP-1 or Wnt/β-catenin or post-translationally by proteolytic activation. MMP-7 expression is low or absent in the healthy kidney, but is significantly upregulated in kidney injury, including AKI and CKD. The function of MMP-7 in kidney disease may differ for CKD and AKI; it may have a profibrotic role in CKD and an anti-apoptotic and regenerative function in AKI. Additionally, the potential of MMP-7 as a biomarker has been studied in different kidney diseases, and the results are promising. Recently, combined unbiased kidney proteomics and transcriptomics approaches identified kidney MMP-7 as the protein having the strongest association with both fibrosis and eGFR and confirmed the predictive role of plasma MMP-7 levels for kidney function decline in over 11 000 individuals. Additionally, urinary MMP-7, combined with urinary cystatin C (CysC) and retinol binding protein (RBP) was reported to provide information on tubular injury in focal segmental glomerulosclerosis and minimal change disease. We now present an overview of research on MMP-7 expression and function in kidney diseases and discuss its potential as a biomarker of kidney diseases.
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尿MMP7作为肾损伤的生物标志物
基质金属蛋白酶7 (MMP-7)是一种分泌的内肽酶,参与细胞外基质成分的降解和细胞因子和生长因子的激活。MMP-7的调控可以通过AP-1或Wnt/β-catenin转录调控,也可以通过翻译后的蛋白水解激活调控。MMP-7在健康肾脏中表达低或不表达,但在肾损伤(包括AKI和CKD)中表达显著上调。MMP-7在CKD和AKI肾脏疾病中的功能可能不同;它可能在CKD中具有促纤维化作用,在AKI中具有抗凋亡和再生功能。此外,已经研究了MMP-7作为不同肾脏疾病的生物标志物的潜力,结果是有希望的。最近,结合无偏倚肾脏蛋白质组学和转录组学方法,发现肾脏MMP-7是与纤维化和eGFR相关性最强的蛋白质,并证实了血浆MMP-7水平对超过11000人肾功能下降的预测作用。此外,尿MMP-7联合尿胱抑素C (CysC)和视黄醇结合蛋白(RBP)被报道为局灶节段性肾小球硬化和微小改变疾病的小管损伤提供信息。我们现在概述了MMP-7在肾脏疾病中的表达和功能的研究,并讨论了其作为肾脏疾病生物标志物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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