Skip to main content
SpringerLink
Log in

Distribution of renal integrin receptors and their ligands in congenital nephrotic syndrome of the finnish type

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

The aim of this study was to examine the distribution of β1 and αv integrins (Ints) and some of their ligands in the kidneys of patients with congenital nephrotic syndrome of the Finnish type (CNF) and in controls using indirect immunofluorescence with monoclonal antibodies. The mesangial reactivity of Int α1 and Int β1 subunits was more variable and an increased glomerular reactivity with Int α3 and Int-α6 antibodies was found in CNF kidneys than in controls. Int α2 subunit was either completely missing from or found in significantly lesser amounts in CNF kidney glomeruli. The immunoreactivity for Int αv was more variable, fainter and also more granular in CNF samples than in control kidneys. The glomerular reactivity for Int β5 was more diffuse and weaker, and in sclerotic Bowman's capsules more intense in CNF kidneys than in controls. Immunoreactivity for Int β6 was restricted and was comparable in extent in CNF and control kidneys. Of the extracellular matrix components studied, the expression of EDAFn, EDBFn, OncFn, Ln α2 chain, Ln β1 chain and tenascin was increased. This is also seen in several glomerular diseases with inflammation and sclerosis. Immunoreactivity for vitronectin was decreased. Several differences were found in the intensity or location of the immunostaining for the β1 and αv Ints and their ligands in CNF kidneys compared with controls, which have not been found in any other proteinuric disease. Disturbed Int expression pattern in CNF may specifically reflect the disturbance of glomerular function caused by the primary defect in this disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Adler S, Eng B (1993) Integrin receptors and function in cultured glomerular endothelial cells. Kidney Int 44:278–284

    Google Scholar 

  2. Ahn C, Tamura R, Yang WS, Lee JS, Quaranta V (1991) Differential expression of integrin α6β1 laminin receptor variants in kidney disease. J Am Soc Nephrol 2:570

    Google Scholar 

  3. Autio-Harmainen H, Rapola J (1983) The thickness of the glomerular basement membrane in congenital nephrotic syndrome of the Finnish type. Nephron 34:48–50

    Google Scholar 

  4. Baraldi A, Furci L, Zambruno G, Rubbiani E, Annessi G, Lusvarghi E (1992) Very late activation-3 integrin is the dominant β1-integrin on the glomerular capillary wall: an immunofluorescence study in nephrotic syndrome. Nephron 62:382–388

    Google Scholar 

  5. Baraldi A, Zambruno G, Furci L, Manca V, Vaschieri C, Lusvarghi E (1994) Beta-1 integrins in the normal human glomerular capillary wall: an immunoelectron microscopy study. Nephron 66:295–301

    Google Scholar 

  6. Breuss JM, Gillett N, Lu L, Sheppard D, Pytela R (1993) Restricted distribution of integrin beta 6 mRNA in primate epithelial tissues. J Histochem Cytochem 41:1521–1527

    Google Scholar 

  7. Bruijn JA, Heer E de (1995) Biology of disease. Adhesion molecules in renal disease. Lab Invest 72:387–394

    Google Scholar 

  8. Cooper HM, Tamura RN, Quaranta V (1991) The major laminin receptor of mouse embryonic stem cells is a novel isoform of the α6β1 integrin. J Cell Biol 115:843–850

    Google Scholar 

  9. Cosio FG (1992) Cell-matrix adhesion receptors: relevance to glomerular pathology. Am J Kidney Dis XX:294–305

    Google Scholar 

  10. Delwel GO, Hogervorst F, Kuikman I, Paulsson M, Timpl R, Sonnenberg A (1993) Expression and function of the cytoplasmic variants of the integrin alpha 6 subunit in transfected K562 cells. Activation-dependent adhesion and interaction with isoforms of laminin. J Biol Chem 268:25865–25875

    Google Scholar 

  11. Delwel GO, Melker AA de, Hogervorst F, Jaspars LH, Fles DLA, Kuikman I, Lindblom A, Paulsson M, Timpl R, Sonnenberg A (1994) Distinct and overlapping ligand specificities of the α3Aβ1 and α6Aβ1 integrins: recognition of laminin isoforms. Mol Biol Cell 5:203–215

    Google Scholar 

  12. Gould VE, Martinez-Lacabe V, Virtanen I, Sahlin KM, Schwartz MM (1992) Differential distribution of tenascin and cellular fibronectins in acute and chronic renal allograft rejection. Lab Invest 67:71–79

    Google Scholar 

  13. Hall DE, Reichardt LF, Crowley E, Holley B, Moezzi H, Sonnenberg A, Damsky CH (1990) The α1/β1 and α6/β1 integrin heterodimers mediate cell attachment to distinct sites on laminin. J Cell Biol 110:2175–2184

    Google Scholar 

  14. Hildebrand J, Schaller M, Parsons JT (1993) Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions. J Cell Biol 123:993–1005

    Google Scholar 

  15. Hogervorst F, Admiraal LG, Niessen C, Kuiman I, Janssen H, Daams H, Sonnenberg A (1993) Biochemical characterization and tissue distribution of the A and B variants of the integrin α6 subunit. J Cell Biol 121:179–191

    Google Scholar 

  16. Holmberg C, Antikainen M, Rönnholm K, Ala-Houhala M, Jalanko H (1995) Management of congenital nephrotic syndrome of the Finnish type. Pediatr Nephrol 9:87–93

    Google Scholar 

  17. Hynes R (1992) Integrins: versatility, modulation, and signalling in cell adhesion. Cell 69:11–25

    Article  CAS  PubMed  Google Scholar 

  18. Kanahara K, Yorioka N, Arita M, Ohira N, Yamakido M (1994) Immunohistochemical studies of extracellular matrix components and integrins in IgA nephropathy. Nephron 66:29–37

    Google Scholar 

  19. Kestilä M, Männikkö M, Holmberg C, Gyapay G, Weissenbach J, Savolainen ER, Peltonen L, Tryggvason K (1994) Congenital nephrotic syndrome of the Finnish type maps to the long arm of chromosome 19. Am J Hum Genet 54:757–764

    Google Scholar 

  20. Kestilä M, Männikkö M, Holmberg C, Korpela K, Savolainen ER, Peltonen L, Tryggvason K (1994) Exclusion of eight genes as mutated loci in congenital nephrotic syndrome of the Finnish type. Kidney Int 45:986–990

    Google Scholar 

  21. Köhler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of pre-defined specificity. Nature 256:495–497

    CAS  PubMed  Google Scholar 

  22. Korhonen M, Ylänne J, Laitinen L, Virtanen I (1990) The α1β6 subunits of integrins are characteristically expressed in distinct segments of developing and adult human nephron. J Cell Biol 111:1245–1254

    Google Scholar 

  23. Korhonen M, Ylänne J, Laitinen L, Virtanen I (1990) Distribution of β1 and β3 integrins in human fetal and adult kidney. Lab Invest 62:616–625

    Google Scholar 

  24. Kriz W, Elger M, Lemley K, Sakai T (1990) Structure of the glomerular mesangium: a biomechanical interpretation. Kidney Int 38 [Suppl 30]:S2–9

    Google Scholar 

  25. Laitinen L, Vartio T, Virtanen I (1991) Cellular fibronectins are differentially expressed in human fetal and adult kidney. Lab Invest 64:492–498

    Google Scholar 

  26. Ljungberg P (1994) Glycosaminoglycans in urine and amniotic fluid in congenital nephrotic syndrome of the Finnish type. Pediatr Nephrol 8:531–536

    Google Scholar 

  27. Ljungberg P, Jalanko H, Holmberg C, Holthofer H (1993) Congenital nephrosis of the Finnish type (CNF): matrix components of the glomerular basement membranes and of cultured mesangial cells. Histochem J 25:606–612

    Google Scholar 

  28. Ljungberg P, Rapola J, Homberg C, Holthöfer H, Jalanko H (1995) Glomerular anionic charge in Congenital nephrotic syndrome of the Finnish type. Histochem J 27:536–546

    Google Scholar 

  29. Ljungberg P, Haltia A, Kuusela P, Jalanko H, Holmberg C, Holthofer H (1995) Noncollagenous matrix components of glomeruli in congenital nephrotic syndrome of the Finnish type (CNF): evidence of abnormal splitting of nidogen in CNF? Exp Nephrol (in press)

  30. Mauch TJ, Vernier RL, Burke BA, Nevins TE (1994) Nephrotic syndrome in the first year of life. In: Holliday MA, Barratt TM, Avner ED (eds) Pediatric nephrology. Williams & Wilkins, Baltimore, pp 788–802

    Google Scholar 

  31. Patey N, Halbwachs-Mecarelli L, Droz D, Lesavre P, Noel LH (1994) Distribution of integrin subunits in normal human kidney. Cell Adhes Commun 2:159–167

    Google Scholar 

  32. Petermann A, Fees H, Grenz H, Goodman SL, Sterzel RB (1993) Polymerase chain reaction and focal contact formation indicate integrin expression in mesangial cells. Kidney Int 44:997–1005

    Google Scholar 

  33. Pöllänen J, Hedman K, Nielsen LS, Dano K, Vaheri A (1988) Ultrastructural localization of plasma membrane-associated urokinase-type plasminogen activator at focal contacts. J Cell Biol 106:87–95

    Google Scholar 

  34. Rapola J (1987) Congenital nephrotic syndrome (Invited review). Pediatr Nephrol 1:441–446

    Google Scholar 

  35. Risteli L, Huttunen NP, Autio-Harmainen H, Risteli J (1982) Slow accumulation of basement membrane collagen in kidney cortex in congenital nephrotic syndrome. Lancet I:712–714

    Google Scholar 

  36. Simon EE, McDonald JA (1990) Extracellular matrix receptors in the kidney cortex. Am J Physiol 259:F783-F792

    Google Scholar 

  37. Sorokin L, Sonnenberg A, Aumailley M, Timpl R, Ekblom P (1990) Recognition of the laminin E8 cell-binding site by an integrin possessing the α6 subunit is essential for epithelial polarization in developing kidney tubules. J Cell Biol 111:1265–1273

    Google Scholar 

  38. Tamura RN, Cooper HM, Collo G, Quaranta V (1991) Cell type-specific integrin variants with alternative α chain cytoplasmic domains. Proc Natl Acad Sci USA 88:10183–10187

    Google Scholar 

  39. Van den Heuvel LPWJ, Van den Born J, Jalanko H, Schröder CH, Veerkamp JH, Assman KJM, Berden JHM, Holmberg C, Rapola J, Monnens LAH (1992) Proteoglycan content of renal basement membranes in the congenital nephrotic syndrome of the Finnish type. Pediatr Nephrol 6:10–15

    Google Scholar 

  40. Vermylen C, Levin M, Mossman J, Barratt TM (1989) Glomerular and urinary heparan sulfate in congenital nephrotic syndrome. Pediatr Nephrol 3:122–129

    Google Scholar 

  41. Vernier RL, Klein DJ, Sisson SP, Mahan JD, Oegema TR, Brown DM (1983) Heparan sulfate-rich anionic sites in the human glomerular basement membrane. Decreased concentration on congenital nephrotic syndrome. N Engl J Med 309:1001–1009

    Google Scholar 

  42. Virtanen I, Laitinen L, Korhonen M (1995) Differential expression of laminin polypeptides in developing and adult human kidney. J Histochem Cytochem 43:621–628

    Google Scholar 

  43. Werb Z, Tremble PM, Behrendtsen O, Crowley E, Damsky CH (1989) Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol 109:877–889

    Google Scholar 

  44. Yamada KM (1991) Fibronectin and other cell interactive glycoproteins. In: Hay ED (ed) Cell biology of extracellular matrix. Plenum Press, New York, pp 111–146

    Google Scholar 

  45. Yatogho T, Izumi M, Kashiwagi H, Hayashi M (1988) Novel purification of vitronectin from human plasma by heparin affinity chromatography. Cell Struct Funct 13:281–292

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, Haartmaninkatu 3, P.O. Box 21, FIN-00014, Helsinki, Finland

    P. Ljungberg & C. Holmberg

  2. Children's Hospital, Helsinki University, Central Hospital, Helsinki, Finland

    H. Jalanko

  3. Institute of Biomedicine, Department of Anatomy, University of Helsinki, Helsinki, Finland

    I. Virtanen

Authors
  1. P. Ljungberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Holmberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Jalanko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. Virtanen
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ljungberg, P., Holmberg, C., Jalanko, H. et al. Distribution of renal integrin receptors and their ligands in congenital nephrotic syndrome of the finnish type. Vichows Archiv A Pathol Anat 428, 333–346 (1996). https://doi.org/10.1007/BF00202200

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00202200

Key words

Search

Navigation