ABSTRACT
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.
Subject(s)
Glucuronidase/biosynthesis , Nitric Oxide Synthase Type III/metabolism , Proteinuria/enzymology , Proteinuria/prevention & control , Albumins/metabolism , Animals , Arginine/analogs & derivatives , Arginine/pharmacology , Doxorubicin/pharmacology , Enzyme Induction/drug effects , Gene Expression Regulation, Enzymologic/drug effects , Glucuronidase/genetics , Mice , Mice, Inbred BALB C , Proteinuria/chemically induced , Proteinuria/geneticsABSTRACT
Renal involvement in systemic lupus erythematosus patients is a severe disease manifestation characterized by various clinical and histopathological alterations. The revised International Society of Nephrology/Renal Pathology Society 2003 classification defines the subclasses of lupus nephritis (LN) according to their pathological glomerular patterns, which has a crucial impact on the prognosis and treatment options for LN patients. There are widely accepted therapeutic agents available, such as cyclophosphamide, mycophenolate mofetil, azathioprine and corticosteroids. Several trials have tried to determine a gold standard for induction and maintenance therapy in LN, and the place of newer drugs, biologicals, has been investigated. We review recently reported data on current treatment regimens in LN, in particular in the context of the International Society of Nephrology/Renal Pathology Society 2003 classification.
