Growth arrest-specific protein 6 protects against renal ischemia-reperfusion injury

Matthew D. Giangola, Weng Lang Yang, Salil R. Rajayer, Michael Kuncewitch, Ernesto Molmenti, Jeffrey Nicastro, Gene F. Coppa, Ping Wang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Background Renal injury caused by ischemia-reperfusion (I/R) often occurs after shock or transplantation. Growth arrest-specific protein 6 (Gas6) is a secreted protein that binds to the TAM - Tyro3, Axl, Mer - family tyrosine kinase receptors, which modulate the inflammatory response and activate cell survival pathways. We hypothesized that Gas6 could have a protective role in attenuating the severity of renal injury after I/R. Materials and methods Adult mice were subjected to 45 min of bilateral renal ischemia. Recombinant mouse Gas6 (rmGas6, 5 μg per mouse) or normal saline (vehicle) was administered intraperitoneally 1 h before ischemia and all subjects were sacrificed at 23 h after I/R for blood and tissue analysis. The expression of protein and messenger RNA (mRNA) was assessed by Western blotting and quantitative polymerase chain reaction, respectively. Results Treatment with rmGas6 significantly decreased serum levels of creatinine and blood urea nitrogen by 29% and 27%, respectively, improved the renal histologic injury index, and reduced the apoptosis in the kidneys, compared with the vehicle. Renal mRNA levels of interleukin 1β, interleukin 6, tumor necrosis factor α, keratinocyte-derived chemokine and macrophage inflammatory protein 2 were decreased significantly by 99%, 60%, 53%, 58%, and 43%, with rmGas6 treatment, respectively. After I/R, renal I-kappa-B α levels were reduced by 40%, whereas they returned to sham levels with rmGas6 treatment. The mRNA levels of inducible nitric oxide synthase and cyclooxygenase 2 were reduced by 79% and 70%, respectively, whereas the expression of cyclin D1 was increased by 2.1-fold in the rmGas6-treated group, compared with the vehicle. Conclusions Gas6 suppresses the nuclear factor κB pathway and promotes cell proliferation, leading to the reduction of inflammation and protection of renal injury induced by I/R.

Original languageEnglish (US)
Pages (from-to)572-579
Number of pages8
JournalJournal of Surgical Research
Volume199
Issue number2
DOIs
StatePublished - Dec 2015

Keywords

  • Apoptosis
  • Gas6
  • Inflammation
  • Ischemia
  • Proliferation
  • Renal
  • Reperfusion

ASJC Scopus subject areas

  • Surgery

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