Title:Dysregulation of Lysyl Oxidases Expression in Diabetic Nephropathy and Renal Cell Carcinoma
Volume: 22
Issue: 17
Author(s): Carolina Añazco*, Sebastián Cerro, Nicolás Pereira, Camila Rojas, Álvaro Torres and Isabel Vidal-Beltrán
Affiliation:
- Biomedical Research Laboratories, Department of Preclinical Sciences, Faculty of Medicine, Universidad Catolica del Maule, Talca,Chile
Keywords:
Cross-linking, renal cell carcinoma, collagen, diabetic nephropathy, endothelial cells, epithelial-mesenchymal transition,
extracellular matrix, glomerular basement membrane, glomerulus, lysyl oxidase, mesangial matrix, podocytes, renal fibrosis.
Abstract: 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.
