title: Podocyte main slit diaphragm proteins, nephrin and podocin, are affected at early stages of lupus nephritis and correlate with disease histology.
abstract: Renal podocytes and their slit diaphragms ensure the integrity of the renal basement membrane that forms the barrier to urinary protein loss. A putative disruption of the slit diaphragm and its main protein components, nephrin and podocin, may be implicated in the pathogenesis of lupus nephritis (LN). We studied the glomerular protein expression of nephrin and podocin in NZB/W LN mice by Western blot and immunofluorescence; mRNA levels were measured by real-time PCR. Human kidney biopsies of class II (n = 5), IV (n = 4), V (n = 7) LN were evaluated for nephrin expression by immunohistochemistry. Glomerular protein expression of nephrin and podocin were significantly reduced in NZB/W LN, starting from the earlier stages (mild mesangial LN) and becoming pronounced at advanced histological forms (focal and diffuse proliferative LN). Nephrin and podocin mRNA levels were substantially decreased in diffuse proliferative disease. Decreased expression of both proteins correlated with electron microscopy findings of distorted slit diaphragms. In patients with LN, nephrin was decreased particularly in diffuse proliferative LN. The main slit diaphragm proteins, nephrin and podocin, are affected from the earlier stages of LN and their expression correlates with disease histology. Our findings suggest a novel role of podocytes and their structures in immune-mediated nephritis.
authors.affiliation: Laboratory of Nephrology, Medical Department, University of Crete, Greece.
authors.forename: G S
authors.initials: GS
authors.lastname: Perysinaki
authors.forename: D K
authors.initials: DK
authors.lastname: Moysiadis
authors.forename: G
authors.initials: G
authors.lastname: Bertsias
authors.forename: I
authors.initials: I
authors.lastname: Giannopoulou
authors.forename: K
authors.initials: K
authors.lastname: Kyriacou
authors.forename: L
authors.initials: L
authors.lastname: Nakopoulou
authors.forename: D T
authors.initials: DT
authors.lastname: Boumpas
authors.forename: E
authors.initials: E
authors.lastname: Daphnis
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D050199:Podocytes / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D012333:RNA, Messenger; C113267:nephrin