Negative impact of recipient SPRED2 deficiency on transplanted lung in a mouse model

Kohei Hashimoto, Masaomi Yamane, Seiichiro Sugimoto, Yutaka Hirano, Takeshi Kurosaki, Shinji Otani, Kentaroh Miyoshi, Toshiaki Ohara, Mikio Okazaki, Teizo Yoshimura, Takahiro Oto, Akihiro Matsukawa, Shinichi Toyooka

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Ischemia-reperfusion injury (IRI) after lung transplantation mainly contributes to the development of primary graft dysfunction. The Sprouty-related EVH1-domain-containing (SPRED) protein family inhibits the mitogen activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway. Our study was aimed at examining the role of SPRED2 in IRI in mice that received orthotopic lung transplantation. Syngeneic mouse lung transplantation was performed in wild-type C57BL/6 J (WT) mice and Spred2 knockout (Spred2−/−) mice on the C57BL/6 J background from the WT donor. Four hours after reperfusion, blood gas analysis was performed, and lung grafts were sacrificed and analyzed. By using arterial oxygen tension measurements and histological evaluation using Lung Injury Score, we revealed more severe IRI in the grafts transplanted to Spred2−/− recipients, which manifested as exacerbated airway epithelial cell damage, interstitial edema with hemorrhage and neutrophil infiltration. Intragraft ERK1/2 activation and expression levels of proinflammatory cytokines and chemokines in Spred2−/− recipients were higher than those in WT recipients. SPRED2 plays an important role in protecting the lungs from IRI in lung transplantation recipients. We suggest that focused treatments suppressing the activity of the MAPK/ERK pathway in transplantation recipients could be the potential therapeutic option for the prevention of lung IRI.

Original languageEnglish
Article number101242
JournalTransplant Immunology
Publication statusPublished - Dec 2019


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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Transplantation


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