TY - JOUR
T1 - Dysregulation of Lysyl Oxidases Expression in Diabetic Nephropathy and Renal Cell Carcinoma
AU - Añazco, Carolina
AU - Cerro, Sebastián
AU - Pereira, Nicolás
AU - Rojas, Camila
AU - Torres, Álvaro
AU - Vidal-Beltrán, Isabel
N1 - Funding Information:
The authors are grateful for the funding by Dirección General de Vinculación of the Universidad Católica del Maule (Grant to Scientific Academy for Medicine Students 243821).
Publisher Copyright:
© 2021 Bentham Science Publishers.
PY - 2021
Y1 - 2021
N2 - Lysyl oxidases (LOXs) are amino oxidase enzymes that catalyze the oxidative deamina-tion 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 compo-nents 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 diseas-es. 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 carcino-ma. The current review summarizes the physiological expression of LOXs enzymes in the nephrons, including glomerulus and tubules. Their roles in renal diseases are particularly highlight-ed 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 bio-marker and pharmacological target to kidney diseases that involves extracellular matrix cross-link-ing 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.
AB - Lysyl oxidases (LOXs) are amino oxidase enzymes that catalyze the oxidative deamina-tion 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 compo-nents 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 diseas-es. 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 carcino-ma. The current review summarizes the physiological expression of LOXs enzymes in the nephrons, including glomerulus and tubules. Their roles in renal diseases are particularly highlight-ed 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 bio-marker and pharmacological target to kidney diseases that involves extracellular matrix cross-link-ing 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.
KW - Collagen
KW - Cross-linking
KW - Diabetic nephropathy
KW - Endothelial cells
KW - Epithelial-mesenchymal tran-sition
KW - Extracellular matrix
KW - Glomerular basement membrane
KW - Glomerulus
KW - Lysyl oxidase
KW - Mesangial matrix
KW - Podocytes
KW - Renal cell carcinoma
KW - Renal fibrosis
UR - http://www.scopus.com/inward/record.url?scp=85122537174&partnerID=8YFLogxK
U2 - 10.2174/1389450122666210712163702
DO - 10.2174/1389450122666210712163702
M3 - Review article
C2 - 34879794
AN - SCOPUS:85122537174
SN - 1389-4501
VL - 22
SP - 1916
EP - 1925
JO - Current Drug Targets
JF - Current Drug Targets
IS - 17
ER -