Osteogenic protein-1 prevents renal fibrogenesis associated with ureteral obstruction

Keith A. Hruska, Guangjie Guo, Magdalena Wozniak, Daniel Martin, Steven Miller, Helen Liapis, Kenneth Loveday, Saulo Klahr, T. Kuber Sampath, Jeremiah Morrissey

Research output: Contribution to journalArticlepeer-review

217 Scopus citations

Abstract

Unilateral ureteral obstruction (UUO) is a model of renal injury characterized by progressive tubulointerstitial fibrosis and renal damage, while relatively sparing the glomerulus and not producing hypertension or abnormalities in lipid metabolism. Tubulointerstitial fibrosis is a major component of several kidney diseases associated with the progression to end-stage renal failure. Here we report that when a critical renal developmental morphogen, osteogenic protein-1 (OP-1; 100 or 300 μg/kg body wt), is administered at the time of UUO and every other day thereafter, interstitial inflammation and fibrogenesis are prevented, leading to preservation of renal function during the first 5 days after obstruction. Compared with angiotensin-converting enzyme inhibition with enalapril treatment, OP-1 was more effective in preventing tubulointerstitial fibrosis and in preserving renal function. The mechanism of OP-1 induced renal protection was associated with prevention of tubular atrophy, an effect not shared with enalapril, and was related to preservation of tubular epithelial integrity. OP-1 blocked the stimulation of epithelial cell apoptosis produced by UUO, which promoted maintenance of tubular epithelial integrity. OP-1 preserved renal blood flow (RBF) during UUO, but enalapril also stimulated RBF. Thus OP-1 treatment inhibited tubular epithelial disruption stimulated by the renal injury of UUO, preventing tubular atrophy and diminishing the activation of tubulointerstitial inflammation and fibrosis and preserving renal function.

Original languageEnglish
Pages (from-to)F130-F143
JournalAmerican Journal of Physiology - Renal Physiology
Volume279
Issue number1 48-1
DOIs
StatePublished - Jul 2000

Keywords

  • Kidney morphogens
  • Renal failure
  • Tubular atrophy
  • Tubulointerstitial fibrosis

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