Rapamycin ameliorates proteinuria and restores nephrin and podocin expression in experimental membranous nephropathy.
OBJECTIVE
Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated.


METHODS
Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in 12 Sprague-Dawley male rats. One week later, six of these rats were commenced on daily treatment with subcutaneous rapamycin 0.5 mgr/kg (PHN-Rapa). The remaining six rats were used as the proteinuric control group (PHN) while six more rats without PHN were given the rapamycin solvent and served as the healthy control group (HC). All rats were sacrificed at the end of the 7th week.


RESULTS
Rapamycin significantly reduced proteinuria during the autologous phase of PHN. Histological lesions were markedly improved by rapamycin. Immunofluorescence revealed attenuated deposits of autologous alloantibodies in treated rats. Untreated rats showed decreased glomerular content of both nephrin and podocin whereas rapamycin restored their expression.


CONCLUSIONS
Rapamycin monotherapy significantly improves proteinuria and histological lesions in experimental membranous nephropathy. This beneficial effect may be mediated by inhibition of the alloimmune response during the autologous phase of PHN and by restoration of the normal expression of the podocyte proteins nephrin and podocin.
Nephrology Department, Heraklion University Hospital, 71110 Heraklion, Greece.
Stavros
S
Stratakis
Kostas
K
Stylianou
Ioannis
I
Petrakis
Vasiliki
V
Mavroeidi
Rafaela
R
Poulidaki
Christina
C
Petra
Demitrios
D
Moisiadis
Spyros
S
Stratigis
Eleftheria
E
Vardaki
Lydia
L
Nakopoulou
Eugene
E
Daphnis
D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects*; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D011507:Proteinuria / Q000188:drug therapy*; D051381:Rats; D020123:Sirolimus / Q000008:administration & dosage / Q000494:pharmacology*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; C113267:nephrin; D020123:Sirolimus