Patterns of nephrin and a new proteinuria-associated protein expression in human renal diseases

Shi Xuan Wang, Maria P. Rastaldi, Anu Pätäri, Heikki Ahola, Eija Heikkilä, Harry Holthöfer

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Background. Many factors contribute to the pathogenesis of glomerular proteinuria, but no exact molecular mechanisms are known to date. The recently reported protein nephrin, encoded by the NPHS1 gene, appears to be crucial for the integrity of the glomerular filtration barrier. Methods. Immunohistochemistry was used to detect possible changes in glomerular nephrin, and a new proteinuria-associated protein expression was developed in various diagnostic groups of human kidney biopsies. Results. In normal control kidney, antibodies to intracellular and extracellular nephrin domain showed a typical podocyte pattern of reactivity, while the 18C7 antibody to a normally inaccessible proteinuria-associated epitope was negative. Instead, strong glomerular positivity by 18C7 was seen in membranous glomerulonephropathy, membranoproliferative glomerulonephritis, systemic lupus erythematosus and cryoglobulinemic nephritis, while with antibodies to either intracellular or extracellular nephrin domains, a down-regulation in nephrin expression pattern was shown. Conclusions. Unmasking or de novo expression of distinct glomerular proteins may be an important feature reflecting the pathophysiological events in these diseases with altered glomerular permeability, while only mild changes in the slit diaphragm protein nephrin appear to take place.

Original languageEnglish (US)
Pages (from-to)141-147
Number of pages7
JournalKidney International
Volume61
Issue number1
DOIs
Publication statusPublished - Jan 1 2002
Externally publishedYes

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Keywords

  • Filtration barrier
  • Glomerular basement membrane
  • Podocytes
  • Slit diaphragm
  • Transmembrane protein

ASJC Scopus subject areas

  • Nephrology

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