Osteopontin modulates angiotensin II-induced inflammation, oxidative stress, and fibrosis of the kidney

Talya Wolak, Hyunju Kim, Yuelan Ren, Jason Kim, Nosratola D. Vaziri, Susanne B. Nicholas

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Osteopontin, a secreted glycoprotein has been implicated in several renal pathological conditions such as those due to ureteral obstruction, ischemia, and cyclosporine toxicity. We studied its possible role in angiotensin II-mediated renal injury by infusing wild-type and osteopontin knockout mice with angiotensin II and found that it raised blood pressure and increased urinary albumin/creatinine ratios in both strains of mice. However, while wild-type mice responded to the infusion by macrophage infiltration and increased expression of α-smooth muscle actin, fibronectin, and transforming growth factor-Β; the osteopontin knockout mice developed none of these. Further, the knockout mice had increased expression of monocyte chemoattractant protein-1; NADPH oxidase subunits such as NOX2, gp47phox, and NOX4; and plasminogen activator inhibitor-1 compared to the wild type animals. Proximal tubule epithelial cells in culture treated with recombinant osteopontin and angiotensin II had increased α-smooth muscle actin and transforming growth factor-Β expression. The effect of angiotensin II was blocked by an antibody to osteopontin. In addition, osteopontin attenuated angiotensin II-induced plasminogen activator inhibitor-1 expression. These studies show that osteopontin is a promoter and an inhibitor of inflammation, oxidative stress, and fibrosis that is capable of modulating angiotensin II-induced renal damage.

Original languageEnglish
Pages (from-to)32-43
Number of pages12
JournalKidney International
Issue number1
StatePublished - 1 Jul 2009
Externally publishedYes


  • Angiotensin II
  • Fibrosis
  • Inflammation
  • Osteopontin
  • Oxidative stress


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