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.
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.
Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.|Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Koichi
K
Suzuki
Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.
Yoshiyasu
Y
Fukusumi
Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.
Mihoko
M
Yamazaki
Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan.
Hiroshi
H
Kaneko
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Kazushi
K
Tsuruga
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Hiroshi
H
Tanaka
Department of Pediatrics, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Etsuro
E
Ito
Department of Internal Medicine IV, Teikyo University School of Medicine, Kawasaki, Japan.
Katsuyuki
K
Matsui
Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Niigata, 951-8510, Japan. kawachi@med.niigata-u.ac.jp.
Hiroshi
H
Kawachi
D000818:Animals; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism*; D009402:Nephrosis, Lipoid / Q000235:genetics* / Q000378:metabolism*; D050199:Podocytes / Q000378:metabolism*; D011692:Puromycin Aminonucleoside / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D000098853:Podoplanin
D008562:Membrane Glycoproteins; D011692:Puromycin Aminonucleoside; C117468:PDPN protein, human; D000098853:Podoplanin
Glycoprotein; Nephrotic syndrome; Podocyte; Proteinuria; Sialic acid