Obstructive nephropathy and renal fibrosis: The role of bone morphogenic protein-7 and hepatocyte growth factor

Saulo Klahr, Jeremiah Morrissey

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83 Scopus citations

Abstract

Background. The nephropathy induced by ureteral obstruction is associated with increased interstitial volume due to matrix deposition, fibroblast differentiation/proliferation, and monocyte infiltration. Recent studies indicate that transforming growth factor-β (TGF-β) is linked to renal fibrosis. Tumor necrosis factor (TNF-α) has a role in the recruitment of inflammatory cells. We found that infiltration of macrophages of the interstitium in unilateral ureteral obstruction (UUO) occurred as early as four hours after the onset of UUO. Methods. Recent studies indicate that a renal tubular development morphogen, bone morphogenetic protein-7 (BMP-7), is effective in preventing the tubulointerstitial nephritis in the setting of obstructive nephropathy. The mechanism of action appears to be preservation of epithelial cell phenotype, inhibition of epithelial-mesenchymal transdifferentiation, and inhibition of injury-induced epithelial cell apoptosis. Hepatocyte growth factor (HGF) also inhibited tubulointerstitial fibrosis. Results. In a treatment protocol in rats with ureteral ligation, BMP-7 restored renal function. The preservation of glomerular filtration rate (GFR) was accompanied by a significant decrease in cortical interstitial volume. In diabetic rats given BMP-7 proteinuria was normalized. In mice with ureteral obstruction, HGF suppressed the expression of TGF-β and of platelet-derived growth factor. The onset of tubulointerstitial fibrosis was almost completely inhibited by HGF. Conclusion. Both BMP-7 and HGF attenuate the tubuloin-terstitial fibrosis due to ureteral obstruction. They also increase GFR and renal plasma flow.

Original languageEnglish
Pages (from-to)S105-S112
JournalKidney International, Supplement
Volume64
Issue number87
DOIs
StatePublished - Nov 2003

Keywords

  • BMP-7
  • ESRD
  • Hepatocyte growth factor
  • Unilateral ureteral obstruction

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