Alteration in the podoplanin–ezrin–cytoskeleton linkage is an important initiation event of the podocyte injury in puromycin aminonucleoside nephropathy, a mimic of minimal change nephrotic syndrome
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Podoplanin was identified as a protein associated with the transformation of arborized foot processes of glomerular epithelial cells (podocytes) to flat feet. However, the function of podoplanin in the podocyte is not yet fully clarified. In this study, we analyzed the molecular nature of podoplanin, and its expression in rat nephrotic models and patients with minimal change nephrotic syndrome (MCNS). We demonstrated here that podoplanin has two forms: one contains abundant sialic acid and the other a lesser amount of sialic acid. Podoplanin bound ezrin to interact with the cytoskeleton. The silencing of podoplanin in cultured podocytes caused a change in the cell shape and the distribution of ezrin and actin. The expression of podoplanin was clearly reduced before the onset of proteinuria in puromycin aminonucleoside (PAN) nephropathy, a mimic of MCNS, and the decrease in the expression of podoplanin became more evident at the proteinuric stage. Podoplanin was detected in normal urine samples, and the amount of urinary podoplanin markedly increased on day 1 of PAN nephropathy. Urinary ezrin was also detected. The amount of the phosphorylated ezrin was reduced, while the amount of the podoplanin-interacting ezrin increased. The podoplanin expression was reduced in a patient with active-phase MCNS. It is conceivable that the alteration of the podoplanin–ezrin–cytoskeleton linkage is an important event of the podocyte injury in MCNS.
KeywordsProteinuria Podocyte Nephrotic syndrome Glycoprotein Sialic acid
This work was supported by Grant-Aids for Scientific Research (B: 23390224 to H.K.) and Grant-Aid for Young Scientists (B: 24790839 to Y.F.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The authors wish to thank Ms. Mutsumi Kayaba and Ms. Yukina Kitazawa for their excellent technical assistance and Mr. Masaaki Nameta for his help in the electron microscopic analysis.
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