J Histochem Cytochem. 2012 Oct 27. [Epub ahead of print] Diabetic Nephropathy and Extracellular Matrix.
Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Oslo, Norway (SOK). 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.
- PMID:
- 23103723
- [PubMed - as supplied by publisher]
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