Añazco Carolina, Cerro Sebastián, Pereira Nicolás, Rojas Camila, Torres Álvaro, Vidal-Beltrán Isabel
Biomedical Research Laboratories, Department of Preclinical Sciences, Faculty of Medicine, Universidad Catolica del Maule, Talca, Chile.
School of Medicine, Faculty of Medicine, Universidad Catolica del Maule, Talca, Chile.
Curr Drug Targets. 2021;22(17):1916-1925. doi: 10.2174/1389450122666210712163702.
Lysyl oxidases (LOXs) are amino oxidase enzymes that catalyze the oxidative deamination of lysine and hydroxylysine residues to form allysine, the first step towards the development of the final cross-linking reaction in collagens, a crucial macromolecule that reinforces extracellular matrices. Basement membranes are specialized extracellular matrices that are essential components of the glomerular filtration barrier, which also support tubular epithelial cells. Lysyl oxidases are post-translational enzymes indispensable for tissue architecture, participating actively in the development and function of kidneys. The differential expression and dysregulation of these enzymes promote diabetic nephropathy, one of the major complications observed in end-stage renal diseases. In addition, these enzymes act as transcription factors that trigger the epithelial-mesenchymal transition responsible for the generation of different cancers. In the kidney, the expression studies in physiological conditions identified LOXL1 and LOXL2 as constituent proteins of glomerular basement membranes. Besides, LOX and LOXL2 are upregulated in fibrosis and renal cell carcinoma. The current review summarizes the physiological expression of LOXs enzymes in the nephrons, including glomerulus and tubules. Their roles in renal diseases are particularly highlighted in diabetic nephropathy and renal cell carcinoma, two pathophysiological conditions where these enzymes have been demonstrated to participate. The focus of the present study is to describe and discuss the current understanding in this field. The current potential of LOXs enzymes as a biomarker and pharmacological target to kidney diseases that involves extracellular matrix cross-linking enzymes is also discussed. LOXs isoforms and their capacity as therapeutic targets could be used for diagnostic and prognostic purposes and in treating these renal complications.
赖氨酰氧化酶（LOXs）是一类氨基氧化酶，可催化赖氨酸和羟赖氨酸残基的氧化脱氨反应，生成醛赖氨酸，这是胶原蛋白最终交联反应发展的第一步，胶原蛋白是强化细胞外基质的关键大分子。基底膜是特殊的细胞外基质，是肾小球滤过屏障的重要组成部分，也支持肾小管上皮细胞。赖氨酰氧化酶是组织架构不可或缺的翻译后修饰酶，积极参与肾脏的发育和功能。这些酶的差异表达和失调会引发糖尿病肾病，这是终末期肾病中观察到的主要并发症之一。此外，这些酶还作为转录因子，触发导致不同癌症产生的上皮-间质转化。在肾脏中，生理条件下的表达研究确定LOXL1和LOXL2是肾小球基底膜的组成蛋白。此外，LOX和LOXL2在纤维化和肾细胞癌中上调。本综述总结了LOXs酶在肾单位（包括肾小球和肾小管）中的生理表达。它们在肾脏疾病中的作用在糖尿病肾病和肾细胞癌中尤为突出，这两种病理生理状况已证明这些酶参与其中。本研究的重点是描述和讨论该领域的当前认识。还讨论了LOXs酶作为涉及细胞外基质交联酶的肾脏疾病生物标志物和药理学靶点的当前潜力。LOXs同工型及其作为治疗靶点的能力可用于诊断和预后目的以及治疗这些肾脏并发症。
