SPRED2 deficiency may lead to lung ischemia–reperfusion injury via ERK1/2 signaling pathway activation

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2 Citations (Scopus)

Abstract

Purpose: Inflammatory changes during lung ischemia–reperfusion injury (IRI) are related to the activation of the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Sprouty-related EVH1 (enabled/vasodilator-stimulated phosphoprotein homology 1)-domain-containing proteins (SPREDs) are known inhibitors of ERK1/2 signaling. The role of SPRED2 in lung IRI was examined in a left hilar clamp mouse model. Methods: C57BL/6 wild-type (WT) and Spred2−/− mice were used in the left hilar clamp model. Experimental groups underwent 30 min of left hilar clamping followed by 1 h of reperfusion. U0126, an ERK1/2 inhibitor, was administered to Spred2−/− mice with reperfused lungs. Results: The partial pressures of oxygen of the Spred2−/− mice after reperfusion were significantly worse than those of WT mice (p < 0.01). Spred2−/− mice displayed more severe injuries than WT mice with increased neutrophil infiltration observed by a histological evaluation and flow cytometry (p < 0.001). This severe inflammation was inhibited by U0126. In addition, the rate of ERK1 activation was significantly higher in the lungs of Spred2−/− mice after reperfusion than in WT mice according to a Western blot analysis (p < 0.05). Conclusion: The activation of the ERK1/2 signaling pathway influences the severity of lung IRI, causing inflammation with neutrophil infiltration. SPRED2 may be a promising target for the suppression of lung IRI.

Original languageEnglish
Pages (from-to)1089-1095
Number of pages7
JournalSurgery today
Volume48
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

Keywords

  • Extracellular signal-regulated kinase
  • Ischemia reperfusion injury
  • Lung transplantation
  • Sprouty-related EVH1 (enabled/vasodilator-stimulated phosphoprotein homology 1)-domain-containing proteins (Spreds)

ASJC Scopus subject areas

  • Surgery

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