BACKGROUND: The recently identified gene NPHS1 with its mutations causing congenital nephrotic syndrome of the Finnish type (CNF) is highly promising in providing new understanding of pathophysiology of proteinuria. Earlier we cloned a rat NPHS1 homologue, as well as characterized and raised antibodies to the respective protein product nephrin. METHODS: Changes in the expression levels of nephrin-specific mRNA in commonly used experimental models of proteinuria were examined using semiquantitative reverse transcription-polymerase chain reaction, immunofluorescence, and immunoelectron microscopy (IEM) of nephrin. RESULTS: Notably, a 40% down-regulation of the nephrin-specific mRNA of cortical kidney was seen already at day 3 after induction of the puromycin aminonucleoside nephrosis (PAN), while no major elevation of urinary protein secretion was seen at this stage. A further decrease of 80% of nephrin message was seen at the peak of proteinuria at day 10. A similar decrease of up to 70% from the basal levels was seen in mercuric chloride-treated rats. Changes in the protein expression paralleled those of the mRNA in indirect immunofluorescence. Interestingly, a remarkable plasmalemmal dislocation from the normal expression site at the interpodocyte filtration slits could be observed in IEM. CONCLUSIONS: Nephrin appears to be an important causative molecule of proteinuria and shows a remarkable redistribution from the filtration slits to the podocyte plasma membrane, especially in PAN.
BACKGROUND: The recently identified gene NPHS1 with its mutations causing congenital nephrotic syndrome of the Finnish type (CNF) is highly promising in providing new understanding of pathophysiology of proteinuria. Earlier we cloned a ratNPHS1 homologue, as well as characterized and raised antibodies to the respective protein product nephrin. METHODS: Changes in the expression levels of nephrin-specific mRNA in commonly used experimental models of proteinuria were examined using semiquantitative reverse transcription-polymerase chain reaction, immunofluorescence, and immunoelectron microscopy (IEM) of nephrin. RESULTS: Notably, a 40% down-regulation of the nephrin-specific mRNA of cortical kidney was seen already at day 3 after induction of the puromycin aminonucleoside nephrosis (PAN), while no major elevation of urinary protein secretion was seen at this stage. A further decrease of 80% of nephrin message was seen at the peak of proteinuria at day 10. A similar decrease of up to 70% from the basal levels was seen in mercuric chloride-treated rats. Changes in the protein expression paralleled those of the mRNA in indirect immunofluorescence. Interestingly, a remarkable plasmalemmal dislocation from the normal expression site at the interpodocyte filtration slits could be observed in IEM. CONCLUSIONS:Nephrin appears to be an important causative molecule of proteinuria and shows a remarkable redistribution from the filtration slits to the podocyte plasma membrane, especially in PAN.
Authors: Kristina M Niculovic; Linda Blume; Henri Wedekind; Elina Kats; Iris Albers; Stephanie Groos; Markus Abeln; Jessica Schmitz; Esther Beuke; Jan H Bräsen; Anette Melk; Mario Schiffer; Birgit Weinhold; Anja K Münster-Kühnel Journal: J Am Soc Nephrol Date: 2019-04-30 Impact factor: 10.121
Authors: Takamoto Ohse; Michael R Vaughan; Jeffrey B Kopp; Ronald D Krofft; Caroline B Marshall; Alice M Chang; Kelly L Hudkins; Charles E Alpers; Jeffrey W Pippin; Stuart J Shankland Journal: Am J Physiol Renal Physiol Date: 2009-12-09
Authors: Liming Wang; Mathew J Ellis; Timothy A Fields; David N Howell; Robert F Spurney Journal: Kidney Blood Press Res Date: 2008-03-27 Impact factor: 2.687