Osteopontin expression in progressive renal injury in remnant kidney: Role of angiotensin II

Xue Q. Yu, Leonard L. Wu, Xiao R. Huang, Niansheng Yang, Richard E. Gilbert, Mark E. Cooper, Richard J. Johnson, Kar N. Lai, Hui Y. Lan

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79 Citations (Scopus)

Abstract

Background. Osteopontin (OPN) is a macrophage chemotactic and adhesion molecule and has been shown to play a role in glomerular and tubulointerstitial injury in several kidney disease models. Methods. The present study examined whether OPN expression is involved in the progression of renal disease following subtotal (5/6) nephrectomy (STNx) in rats and whether angiotensin II (Ang II) mediates the up-regulation of renal OPN expression and macrophage accumulation in this model by administering valsartan, an Ang II type I (AT1) receptor antagonist, or ramipril, an angiotensin-converting enzyme (ACE) inhibitor. Results. In normal and sham-operated rat kidneys, OPN was expressed in a few tubules (< 5%) and was absent in glomeruli. Following STNx (weeks 2 to 16), there was substantial up-regulation of OPN mRNA and protein expression in glomeruli [2 to 12 cells/glomerular cross section (gcs)] and tubular epithelial cells (20 to 75% OPN+). The up-regulation of OPN expression was associated with macrophage accumulation within the kidney, severe proteinuria, loss of renal function, and severe histologic damage, including tubulitis and tubulointerstitial fibrosis (all P < 0.001). Treatment with either valsartan or ramipril completely abrogated the up-regulation of OPN mRNA and protein expression in glomeruli and tubules. The reduction in OPN expression was associated with a significant inhibition of macrophage accumulation and progressive renal injury (P < 0.001). Conclusion. An up-regulation of OPN expression may play a role in progressive renal injury following STNx. Inhibition of OPN expression may be one of the mechanisms by which Ang II blockade attenuated renal injury after renal ablation.

Original languageEnglish
Pages (from-to)1469-1480
Number of pages12
JournalKidney International
Volume58
Issue number4
DOIs
Publication statusPublished - 1 Jan 2000
Externally publishedYes

Keywords

  • Adhesion molecule
  • Macrophages
  • Nephrectomy
  • Rampiril
  • Tubulointerstitial injury
  • Valsartan

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