Endothelin-1 induces proteinuria by Heparanase-mediated disruption of the glomerular glycocalyx

Garssen, Marjolein

Marjolein Garsen (photo up) and Johan van der Vlag, theme Renal Disorders identified a novel mechanism that contributes to the development of proteinuria during Diabetic Nephropathy (DN). In a set of experiments Marjolein Garsen and collaborators show that diabetes-induced endothelin-1 signaling subsequently induces the expression of the heparan sulfate- degrading enzyme heparanase. Heparanase then mediates the degradation of the glycocalyx, the development of proteinuria and renal failure. The identified mechanism may explain the beneficial effects of endothelin-1 receptor blockers in DN.

The results of this study and a parallel study have been published in the highest ranking journal for kidney research, the Journal of the American Society of Nephrology (link) and the high ranking journal Diabetes (link). 

Based on these and other studies by Johan van der Vlag and co-workers during the last decade, heparanase represents a bona fide therapeutic target to treat glomerular diseases.


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