title: Early treatment with glucocorticoids or cyclophosphamide retains the slit diaphragm proteins nephrin and podocin in experimental lupus nephritis.
abstract: Renal podocytes and their slit diaphragms ensure the integrity of renal basement membrane and prevent urinary protein loss. We have previously reported that decreases of the podocyte slit diaphragm proteins nephrin and podocin represent early events in the podocytopathy of lupus nephritis (LN). We asked whether immunosuppressive agents such as glucocorticoids and cyclophosphamide may have direct effects on podocytes. We assessed in New Zealand Black/New Zealand White (NZB/W) F1 LN mice glomerular nephrin and podocin expression and localization by the use of Western blot and immunofluorescence; mRNA levels were measured by real-time polymerase chain reaction (PCR) and renal histology by light and electron microscopy. Early treatment with glucocorticoids and cyclophosphamide halted the histologic alterations associated with LN, preserving podocyte foot processes. Nephrin and podocin protein expression significantly increased in both glucocorticoid and cyclophosphamide groups as early as after three months of therapy. Real-time PCR revealed similar enhancement in nephrin and podocin mRNA levels after three to six months of treatment. This study documents that early treatment in experimental LN with glucocorticoids or cyclophosphamide preserves slit diaphragm proteins in podocytes and halts histological changes of the glomeruli, thus raising the possibility of a direct protective effect of these drugs on podocytes.
authors: Laboratory of Nephrology, Medical Department, University of Crete, Greece.
authors: D K
authors: DK
authors: Moysiadis
authors: G S
authors: GS
authors: Perysinaki
authors: G
authors: G
authors: Bertsias
authors: S
authors: S
authors: Stratakis
authors: K
authors: K
authors: Kyriacou
authors: L
authors: L
authors: Nakopoulou
authors: D T
authors: DT
authors: Boumpas
authors: E
authors: E
authors: Daphnis
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003520:Cyclophosphamide / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008814:Mice, Inbred NZB; D050199:Podocytes / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D012333:RNA, Messenger; C113267:nephrin; D003520:Cyclophosphamide