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Stem cell factor in a rat model of serum nephrotoxic nephritis.

AbstractBACKGROUND:
Stem cell factor (SCF) has been implicated in many disease processes characterized by tissue remodelling and fibrosis. The growth factor (SCF) was evaluated in a rat model of nephrotoxic serum nephritis (NTN), characterized by early inflammation followed by later tissue fibrosis.
METHODS:
NTN was induced in male Wistar Kyoto rats using rabbit anti-rat glomerular basement membrane antibodies. Animals were sacrificed at days 7, 15, 30 and 45 (n = 4-10 per group). Rats' kidneys were immunostained for ED1 as marker of inflammation, CD34, SCF, c-kit, mast cell tryptase and markers of fibrosis; collagens III and IV and alpha-SMA. Changes in SCF protein and mRNA content were evaluated by Western blotting and Northern blotting, respectively.
RESULTS:
In the NTN kidney, levels of immunoreactive SCF and SCF receptor (c-kit) were significantly higher in glomerular, tubular and interstitial compartments. Mast cells were barely detectable in NTN and control rat sections. Double immunostaining showed the co-localization of SCF with alpha-SMA and of the SCF receptor with CD34 and ED1 positive cells. Immunostainable SCF protein in each of the 3 compartments, glomerular, tubular and interstitial, showed a positive linear correlation with serum creatinine, proteinuria, glomerulosclerosis score and interstitial fibrosis scores. Using multivariate analysis, immunostainable tubular SCF was a predictor of glomerular sclerosis and immunostainable glomerular SCF predicted tubular atrophy. Increased SCF immunostain was not a consequence of altered transcription as there was a fall in SCF mRNA determined by Northern blotting. Western blotting of NTN kidney homogenates revealed two bands for SCF, a 43-kDa band which decreased, and a 19-kDa band which increased throughout the study.
CONCLUSION:
These results highlight the potential role of SCF and its receptor in the remodelling process of the NTN kidney. Upregulation of SCF may involve a translational mechanism, with the soluble SCF protein KL-S1 (19 kDa) being derived from the transmembrane SCF protein KL-1 (43 kD) by proteolytic cleavage. The immunohistochemical staining of few CD34+ cells in NTN kidneys warrants further evaluation of the nature of these cells in the context of the inflammatory as well as the fibrotic processes.
AuthorsM M El Kossi, J L Haylor, T S Johnson, A M El Nahas
JournalNephron. Experimental nephrology (Nephron Exp Nephrol) Vol. 108 Issue 1 Pg. e1-e10 ( 2008) ISSN: 1660-2129 [Electronic] Switzerland
PMID18087173 (Publication Type: Comparative Study, Journal Article)
Copyright(c) 2007 S. Karger AG, Basel
Chemical References
  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit
Topics
  • Animals
  • Disease Models, Animal
  • Glomerulonephritis (blood, genetics, pathology)
  • Male
  • Proteinuria (blood, genetics, pathology)
  • Proto-Oncogene Proteins c-kit (biosynthesis, blood, genetics)
  • Rats
  • Rats, Inbred WKY
  • Stem Cell Factor (biosynthesis, blood, genetics)

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