論文

査読有り
2018年12月

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

Surgery today
  • Masanori Okada
  • ,
  • Masaomi Yamane
  • ,
  • Sumiharu Yamamoto
  • ,
  • Shinji Otani
  • ,
  • Kentaroh Miyoshi
  • ,
  • Seiichiro Sugimoto
  • ,
  • Akihiro Matsukawa
  • ,
  • Shinichi Toyooka
  • ,
  • Takahiro Oto
  • ,
  • Shinichiro Miyoshi

48
12
開始ページ
1089
終了ページ
1095
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/s00595-018-1696-x

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.

リンク情報
DOI
https://doi.org/10.1007/s00595-018-1696-x
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30022248
ID情報
  • DOI : 10.1007/s00595-018-1696-x
  • ISSN : 0941-1291
  • PubMed ID : 30022248

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