Osteopontin blockade attenuates renal injury after ischemia reperfusion by inhibiting NK cell infiltration

Cindy Cen, Monowar Aziz, Weng Lang Yang, Jeffrey M. Nicastro, Gene F. Coppa, Ping Wang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Renal ischemia-reperfusion (RIR) injury is a common occurrence after major surgery and shock, leading to acute kidney injury (AKI). Osteopontin (OPN) is a secreted glycoprotein that acts as a proinflammatory cytokine and activator of T lymphocytes. We hypothesized that blockade of OPN reduces the severity of inflammation and injury in RIR. Renal ischemia was induced in adult C57BL/6 mice via bilateral clamping of renal pedicles for 35 min, followed by reperfusion for 24 h. Anti-OPN antibody (Ab), nonimmunized isotype immunoglobulin G, or normal saline was injected intravenously at the time of reperfusion. Blood and kidneys were collected for analysis. At 24 h after RIR, OPN mRNA and protein levels were significantly increased in renal tissue compared with sham mice. In serum, elevated levels of blood urea nitrogen and creatinine were reduced in anti-OPN Ab-treated mice compared with vehicle. Anti-OPN Ab-treated mice also had decreased mRNA levels of injury markers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 compared with the vehicle. The histologic architecture and apoptosis of renal tissue were improved in the anti-OPN Ab-treated mice. In renal tissue, inflammatory cytokines interleukin 6 and tumor necrosis factor-a protein levels were reduced in the Ab-treated mice. Natural killer (NK) cell infiltration was decreased after anti-OPN Ab treatment, as was neutrophil infiltration, shown by reduced chemokine expression and Gr1 renal immunohistochemical staining. These findings demonstrate a beneficial role of OPN blockade in RIR associated with NK cell-mediated downregulation of inflammatory cytokines and chemokines. Administration of anti-OPN Ab may therefore serve as an immunomodulatory adjunct in the treatment of RIR-induced AKI.

Original languageEnglish (US)
Pages (from-to)52-60
Number of pages9
Issue number1
StatePublished - Jan 1 2017
Externally publishedYes


  • Acute kidney injury
  • Apoptosis
  • Inflammation
  • NK cells
  • Neutrophils

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine


Dive into the research topics of 'Osteopontin blockade attenuates renal injury after ischemia reperfusion by inhibiting NK cell infiltration'. Together they form a unique fingerprint.

Cite this