赖氨酰氧酶在糖尿病肾病和肾细胞癌中的表达失调

Title:Dysregulation of Lysyl Oxidases Expression in Diabetic Nephropathy and Renal Cell Carcinoma

Volume: 22 Issue: 17

关键词: 交联、肾细胞癌、胶原蛋白、糖尿病肾病、内皮细胞、上皮间质转化、细胞外基质、肾小球基底膜、肾小球、赖氨酰氧化酶、系膜基质、足细胞、肾纤维化。

摘要: 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.

Cite this article as:

Dysregulation of Lysyl Oxidases Expression in Diabetic Nephropathy and Renal Cell Carcinoma, Current Drug Targets 2021; 22 (17) . https://dx.doi.org/10.2174/1389450122666210712163702