TY - JOUR
T1 - Endothelial nitric oxide synthase prevents heparanase induction and the development of proteinuria
AU - Garsen, Marjolein
AU - Rops, Angelique L.
AU - Li, Jinhua
AU - Van Beneden, Katrien
AU - Van Den Branden, Christiane
AU - Berden, Jo H.M.
AU - Rabelink, Ton J.
AU - Van Der Vlag, Johan
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Endothelial nitric oxide synthase (eNOS) deficiency exacerbates proteinuria and renal injury in several glomerular diseases, but the underlying mechanism is not fully understood. We recently showed that heparanase is essential for the development of experimental diabetic nephropathy and glomerulonephritis, and hypothesize that heparanase expression is regulated by eNOS. Here, we demonstrate that induction of adriamycin nephropathy (AN) in C57BL/6 eNOS-deficient mice leads to an increased glomerular heparanase expression accompanied with overt proteinuria, which was not observed in the AN-resistant wild type counterpart. In vitro, the eNOS inhibitor asymmetric dimethylarginine (ADMA) induced heparanase expression in cultured mouse glomerular endothelial cells. Moreover, ADMA enhanced transendothelial albumin passage in a heparanase-dependent manner. We conclude that eNOS prevents heparanase induction and the development of proteinuria.
AB - Endothelial nitric oxide synthase (eNOS) deficiency exacerbates proteinuria and renal injury in several glomerular diseases, but the underlying mechanism is not fully understood. We recently showed that heparanase is essential for the development of experimental diabetic nephropathy and glomerulonephritis, and hypothesize that heparanase expression is regulated by eNOS. Here, we demonstrate that induction of adriamycin nephropathy (AN) in C57BL/6 eNOS-deficient mice leads to an increased glomerular heparanase expression accompanied with overt proteinuria, which was not observed in the AN-resistant wild type counterpart. In vitro, the eNOS inhibitor asymmetric dimethylarginine (ADMA) induced heparanase expression in cultured mouse glomerular endothelial cells. Moreover, ADMA enhanced transendothelial albumin passage in a heparanase-dependent manner. We conclude that eNOS prevents heparanase induction and the development of proteinuria.
UR - http://www.scopus.com/inward/record.url?scp=84983643565&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0160894
DO - 10.1371/journal.pone.0160894
M3 - Article
C2 - 27505185
AN - SCOPUS:84983643565
SN - 1932-6203
VL - 11
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e0160894
ER -
