Diabetic Nephropathy and Extracellular Matrix |
| |
Authors: | S O Kolset F P Reinholt T Jenssen |
| |
Institution: | Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Oslo, Norway (SOK);Department of Pathology, University of Oslo and Oslo University Hospital–Rikshospitalet, Oslo, Norway (FPR);Section of Renal Diseases, Department of Organ Transplantation, Oslo University Hospital–Rikshospitalet, Oslo, Norway (TJ);Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway (TJ) |
| |
Abstract: | Diabetic nephropathy (DN) is a serious complication in diabetes. Major typical
morphological changes are the result of changes in the extracellular matrix (ECM). Thus,
basement membranes are thickened and the glomerular mesangial matrix and the
tubulointerstitial space are expanded, due to increased amounts of ECM. One important ECM
component, the proteoglycans (PGs), shows a more complex pattern of changes in DN. PGs in
basement membranes are decreased but increased in the mesangium and the tubulointerstitial
space. The amounts and structures of heparan sulfate chains are changed, and such changes
affect levels of growth factors regulating cell proliferation and ECM synthesis, with cell
attachment affecting endothelial cells and podocytes. Enzymes modulating heparan sulfate
structures, such as heparanase and sulfatases, are implicated in DN. Other enzyme classes
also modulate ECM proteins and PGs, such as matrix metalloproteinases (MMPs) and serine
proteases, such as plasminogen activator, as well as their corresponding inhibitors. The
levels of these enzymes and inhibitors are changed in plasma and in the kidneys in DN.
Several growth factors, signaling pathways, and hyperglycemia per se affect ECM synthesis
and turnover in DN. Whether ECM components can be used as markers for early kidney changes
is an important research topic, whereas at present, the clinical use remains to be
established. |
| |
Keywords: | extracellular matrix glycoconjugates molecular pathology MMP fibrosis |
|
|