Extracellular matrix metabolism in diabetic nephropathy.
Diabetic nephropathy is characterized by excessive deposition of extracellular matrix proteins in the mesangium and basement membrane of the glomerulus and in the renal tubulointerstitium. This review summarizes the main changes in protein composition of the glomerular mesangium and basement membrane and the evidence that, in the mesangium, these are initiated by changes in glucose metabolism and the formation of advanced glycation end products. Both processes generate reactive oxygen species (ROS). The review includes discussion of how ROS may activate intracellular signaling pathways leading to the activation of redox-sensitive transcription factors. This in turn leads to change in the expression of genes encoding extracellular matrix proteins and the protease systems responsible for their turnover.
Mason
Roger M
RM
Cell and Molecular Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK. roger.mason@imperial.ac.uk
Wahab
Nadia Abdel
NA
D000818:Animals; D003928:Diabetic Nephropathies / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000378:metabolism*; D006801:Humans
D016326:Extracellular Matrix Proteins