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Glomerular albumin filtration through podocyte cell body in puromycin aminonucleoside nephrotic rat

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Abstract

It is an a priori concept that protein molecules including albumin are filtrated through the slit membrane between the foot processes of podocytes. However, foot processes are effaced and the number of slit membranes is reduced in nephrotic syndrome, suggesting another pathway of albumin filtration through the foot process cell body. Thus, we investigated the pathway of gold-and fluorescein isothiocyanate (FITC)-labeled albumin filtration in the puromycin aminonucleoside (PAN) model of nephrotic syndrome in the rat. PAN rats at day 7 with established nephrotic proteinuria were injected with 8-nm gold-labeled albumin and FITC-labeled albumin through the jugular vein followed by kidney fixation at 10 or 30 min. Goldlabeled albumin was accumulated in the paramesangial area and in the endosomes of glomerular endothelial cells of both control and PAN rats by electron microscopy. On the other hand, FITC-labeled albumin was detected between foot processes in the control but more in the podocyte cell body in the PAN rat. In conclusion, albumin will be filtrated through the decreased numbers of slit diaphragms; however, albumin can be also taken up in the podocyte, the mesangium, and the glomerular endothelium, suggesting that there might be other routes of glomerular albumin clearance in nephrotic syndrome.

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References

  1. Farquhar MG (2006) the glomerular basement membrane: not gone, just forgotten. J Clin Invest 116:2090–2093

    Article  PubMed  CAS  Google Scholar 

  2. Farquhar MG, Wissig SL, Palade GE (1961) Glomerular permeability. I. Ferritin transfer across the normal glomerular capillary wall. J Exp Med 113:47–66

    Article  PubMed  CAS  Google Scholar 

  3. Farquhar MG, Palade GE (1961) Glomerular permeability. II. Ferritin transfer across the glomerular capillary wall in nephrotic rats. J Exp Med 114:699–716

    Article  PubMed  CAS  Google Scholar 

  4. Ryan GB, Rodewald R, Karnovsky MJ (1975) An ultrastructural study of the glomerular slit diaphragm in aminonucleoside nephrosis. Lab Invest 33:461–468

    PubMed  CAS  Google Scholar 

  5. Rodewald R, Karnovsky MJ (1974) Porous substructure of the glomerular slit diaphragm in the rat and mouse. J Cell Biol 60:423–433

    Article  PubMed  CAS  Google Scholar 

  6. Deen WM (2004) What determines glomerular capillary permeability? J Clin Invest 114:1412–1414

    PubMed  CAS  Google Scholar 

  7. Tryggvason K (1999) Unraveling the mechanisms of glomerular ultrafiltration: nephrin, a key component of the slit diaphragm. J Am Soc Nephrol 10:2440–2445

    PubMed  CAS  Google Scholar 

  8. Ruotsalainen V, Ljungberg P, Wartiovaara J, Lenkkeri U, Kestilä M, Jalanko H, Holmberg C, Tryggvason K (1999) Nephrin is specifically located at the slit diaphragm of glomerular podocytes. Proc Natl Acad Sci U S A 96:7962–7967

    Article  PubMed  CAS  Google Scholar 

  9. Kwoh C, Shannon MB, Miner JH, Shaw A (2006) Pathogenesis of nonimmune glomerulopathies. Annu Rev Pathol 1:349–374

    Article  PubMed  CAS  Google Scholar 

  10. Kawachi H, Miyauchi N, Suzuki K, Han GD, Orikasa M, Shimizu F (2006) Role of podocyte slit diaphragm as a filtration barrier. Nephrology (Carlton) 11:274–281

    Article  CAS  Google Scholar 

  11. Wartiovaara J, Ofverstedt LG, Khoshnoodi J, Zhang J, Mäkelä E, Sandin S, Ruotsalainen V, Cheng RH, Jalanko H, Skoglund U, Tryggvason K (2004) Nephrin strands contribute to a porous slit diaphragm scaffold as revealed by electron tomography. J Clin Invest 114:1475–1483

    PubMed  CAS  Google Scholar 

  12. Jarad G, Cunningham J, Shaw AS, Miner JH (2006) Proteinuria precedes podocyte abnormalities in Lamb2-/-mice, implicating the glomerular basement membrane as an albumin barrier. J Clin Invest 116:2272–2279

    Article  PubMed  CAS  Google Scholar 

  13. Lahdenkari AT, Lounatmaa K, Patrakka J, Holmberg C, Wartiovaara J, Kestilä M, Koskimies O, Jalanko H (2004) Podocytes are firmly attached to glomerular basement membrane in kidneys with heavy proteinuria. J Am Soc Nephrol 15:2611–2618

    Article  PubMed  Google Scholar 

  14. Patrakka J, Lahdenkari AT, Koskimies O, Holmberg C, Wartiovaara J, Jalanko H (2002) The number of podocyte slit diaphragms is decreased in minimal change nephrotic syndrome. Pediatr Res 52:349–355

    PubMed  Google Scholar 

  15. Heckel K, Kiefmann R, Dörger M, Stoeckelhuber M, Goetz AE (2004) Colloidal gold particles as a new in vivo marker of early acute lung injury. Am J Physiol Lung Cell Mol Physiol 287:L867–L878

    Article  PubMed  CAS  Google Scholar 

  16. Tojo A, Onozato ML, Kurihara H, Sakai T, Goto A, Fujita T (2003) Angiotensin II blockade restores albumin reabsorption in the proximal tubules of diabetic rats. Hypertens Res 26:413–419

    Article  PubMed  CAS  Google Scholar 

  17. Tojo A, Onozato ML, Fukuda S, Asaba K, Kimura K, Fujita T (2004) Nitric oxide generated by nNOS in the macula densa regulates the afferent arteriolar diameter in rat kidney. Med Electron Microsc 37:236–241

    Article  PubMed  CAS  Google Scholar 

  18. Tojo A, Onozato ML, Ha H, Kurihara H, Sakai T, Goto A, Fujita T, Endou H (2001) Reduced albumin reabsorption in the proximal tubule of early-stage diabetic rats. Histochem Cell Biol 116:269–276

    PubMed  CAS  Google Scholar 

  19. Tojo A, Bredt DS, Wilcox CS (1999) Distribution of postsynaptic density proteins in rat kidney: relationship to neuronal nitric oxide synthase. Kidney Int 55:1384–1394

    Article  PubMed  CAS  Google Scholar 

  20. Jeansson M, Haraldsson B (2006) Morphological and functional evidence for an important role of the endothelial cell glycocalyx in the glomerular barrier. Am J Physiol Renal Physiol 290:F111–F116

    Article  PubMed  CAS  Google Scholar 

  21. Ryan GB, Karnovsky MJ (1976) Distribution of endogenous albumin in the rat glomerulus: role of hemodynamic factors in glomerular barrier function. Kidney Int 9:36–45

    Article  PubMed  CAS  Google Scholar 

  22. Tojo A, Endou H (1992) Intrarenal handling of proteins in rats using fractional micropuncture technique. Am J Physiol 263:F601–F606

    PubMed  CAS  Google Scholar 

  23. Maack T, Park CH (1990) Endocytosis and lysosomal hydrolysis of proteins in proximal tubules. Methods Enzymol 191:340–354

    Article  PubMed  CAS  Google Scholar 

  24. Park CH, Maack T (1984) Albumin absorption and catabolism by isolated perfused proximal convoluted tubules of the rabbit. J Clin Invest 73:767–777

    Article  PubMed  CAS  Google Scholar 

  25. Oken DE, Flamenbaum W (1971) Micropuncture studies of proximal tubule albumin concentrations in normal and nephrotic rats. J Clin Invest 50:1498–1505

    Article  PubMed  CAS  Google Scholar 

  26. Caulfield JP, Farquhar MG (1975) The permeability of glomerular capillaries of aminonuceoside nephrotic rats to graded dextrans. J Exp Med 142:61–83

    Article  PubMed  CAS  Google Scholar 

  27. Ohba S, Kimura K, Mise N, Konno Y, Suzuki N, Miyashita K, Tojo A, Hirata Y, Uehara Y, Atarashi K, Goto A, Omata M (1997) Differential localization of s and e antigens in hepatitis B virus-associated glomerulonephritis. Clin Nephrol 48:44–47

    PubMed  CAS  Google Scholar 

  28. Eyre J, Joannou K, Grubb BD, Saleem MA, Mathieson PW, Brunskill NJ, Christensen EI, Topham PS (2007) Statin-sensitive endocytosis of albumin by glomerular podocytes. Am J Physiol Renal Physiol 292:F674–F681

    Article  PubMed  CAS  Google Scholar 

  29. Birn H, Fyfe JC, Jacobsen C, Mounier F, Verroust PJ, Orskov H, Willnow TE, Moestrup SK, Christensen EI (2000) Cubilin is an albumin binding protein important for renal tubular albumin reabsorption. J Clin Invest 105:1353–1361

    Article  PubMed  CAS  Google Scholar 

  30. Bohrer MP, Baylis C, Robertson CR, Brenner BM, Troy JL, Willis WT (1977) Mechanisms of the puromycin-induced defects in the transglomerular passage of water and macromolecules. J Clin Invest 60:152–161

    Article  PubMed  CAS  Google Scholar 

  31. Brenner BM, Hostetter TH, Humes HD (1978) Glomerular perm-selectivity: barrier function based on discrimination of molecular size and charge. Am J Physiol 234:F455–F460

    PubMed  CAS  Google Scholar 

  32. Olson JL, Rennke HG, Venkatachalam MA (1981) Alterations in the charge and size selectivity barrier of the glomerular filter in aminonucleoside nephrosis in rats. Lab Invest 44:271–279

    PubMed  CAS  Google Scholar 

  33. Kawachi H, Koike H, Kurihara H, Yaoita E, Orikasa M, Shia MA, Sakai T, Yamamoto T, Salant DJ, Shimizu F (2000) Cloning of rat nephrin: expression in developing glomeruli and in proteinuric states. Kidney Int 57:1949–1961

    Article  PubMed  CAS  Google Scholar 

  34. Ina K, Kitamura H, Tatsukawa S, Takayama T, Fujikura Y (2002) Glomerular podocyte endocytosis of the diabetic rat. J Electron Microsc (Tokyo) 51:275–279

    Article  CAS  Google Scholar 

  35. Whiteside CI, Cameron R, Munk S, Levy J (1993) Podocytic cytoskeletal disaggregation and basement-membrane detachment in puromycin aminonucleoside nephrosis. Am J Pathol 142:1641–1653

    PubMed  CAS  Google Scholar 

  36. Yu D, Petermann A, Kunter U, Rong S, Shankland SJ, Floege J (2005) Urinary podocyte loss is a more specific marker of ongoing glomerular damage than proteinuria. J Am Soc Nephrol 16:1733–1741

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Nephrology and Endocrinology, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Akihiro Tojo, Maristela Lika Onozato, Satoshi Kinugasa, Satoru Fukuda & Toshiro Fujita

  2. Division of Nephrology and Hypertension, Cardiovascular Kidney Institute, Georgetown University, Washington DC, USA

    Maristela Lika Onozato

  3. Renal Division, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

    Chagriya Kitiyakara

  4. Electron Microscope Application Laboratory, Saitama, Japan

    Toshio Sakai

Authors
  1. Akihiro Tojo
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  2. Maristela Lika Onozato
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  3. Chagriya Kitiyakara
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  4. Satoshi Kinugasa
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  5. Satoru Fukuda
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  6. Toshio Sakai
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  7. Toshiro Fujita
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Correspondence to Akihiro Tojo.

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Tojo, A., Onozato, M.L., Kitiyakara, C. et al. Glomerular albumin filtration through podocyte cell body in puromycin aminonucleoside nephrotic rat. Med Mol Morphol 41, 92–98 (2008). https://doi.org/10.1007/s00795-008-0397-8

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  • DOI: https://doi.org/10.1007/s00795-008-0397-8

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