The role of heparanase in diseases of the glomeruli.
The glomerular basement membrane (GBM) is a kind of net that remains in a state of dynamic equilibrium. Heparan sulfate proteoglycans (HSPGs) are among its most important components. There are much data indicating the significance of these proteoglycans in protecting proteins such as albumins from penetrating to the urine, although some new data indicate that loss of proteoglycans does not always lead to proteinuria. Heparanase is an enzyme which cleaves beta 1,4 D: -glucuronic bonds in sugar groups of HSPGs. Thus it is supposed that heparanase may have an important role in the pathogenesis of proteinuria. Increased heparanase expression and activity in the course of many glomerular diseases was observed. The most widely documented is the significance of heparanase in the pathogenesis of diabetic nephropathy. Moreover, heparanase acts as a signaling molecule and may influence the concentrations of active growth factors in the GBM. It is being investigated whether heparanase inhibition may cause decreased proteinuria. The heparanase inhibitor PI-88 (phosphomannopentaose sulfate) was effective as an antiproteinuric drug in an experimental model of membranous nephropathy. Nevertheless, this drug is burdened by some toxicity, so further investigations should be considered.
Szymczak
Maciej
M
Department of Nephrology and Transplantation Medicine, Wrocław Medical University, Traugutta 57/59, Wrocław, Poland. mszymc@wp.pl
Kuźniar
Jakub
J
Klinger
Marian
M
D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic; D050533:Glomerular Basement Membrane / Q000378:metabolism / Q000473:pathology; D005966:Glucuronidase / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D009844:Oligosaccharides / Q000009:adverse effects / Q000627:therapeutic use; D011507:Proteinuria; D015398:Signal Transduction; D000099175:Heparanase
D005966:Glucuronidase; D019812:Heparan Sulfate Proteoglycans; D009844:Oligosaccharides; D000099175:Heparanase; C120158:phosphomannopentaose sulfate