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

Research output: Contribution to journalArticle

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
JournalSurgery Today
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

MAP Kinase Signaling System
Lung Injury
Reperfusion
Neutrophil Infiltration
Inflammation
Lung
Mitogen-Activated Protein Kinase 3
Partial Pressure
Mitogen-Activated Protein Kinase 1
Constriction
Flow Cytometry
Western Blotting
Oxygen
Wounds and Injuries

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

Cite this

@article{2a15ade3944947fc9df9cacb13bed52f,
title = "SPRED2 deficiency may lead to lung ischemia–reperfusion injury via ERK1/2 signaling pathway activation",
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.",
keywords = "Extracellular signal-regulated kinase, Ischemia reperfusion injury, Lung transplantation, Sprouty-related EVH1 (enabled/vasodilator-stimulated phosphoprotein homology 1)-domain-containing proteins (Spreds)",
author = "Masanori Okada and Masaomi Yamane and Sumiharu Yamamoto and Shinji Otani and Kentaroh Miyoshi and Seiichiro Sugimoto and Akihiro Matsukawa and Shinichi Toyooka and Takahiro Oto and Shinichiro Miyoshi",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00595-018-1696-x",
language = "English",
journal = "Japanese Journal of Surgery",
issn = "0941-1291",
publisher = "Springer Japan",

}

TY - JOUR

T1 - SPRED2 deficiency may lead to lung ischemia–reperfusion injury via ERK1/2 signaling pathway activation

AU - Okada, Masanori

AU - Yamane, Masaomi

AU - Yamamoto, Sumiharu

AU - Otani, Shinji

AU - Miyoshi, Kentaroh

AU - Sugimoto, Seiichiro

AU - Matsukawa, Akihiro

AU - Toyooka, Shinichi

AU - Oto, Takahiro

AU - Miyoshi, Shinichiro

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Extracellular signal-regulated kinase

KW - Ischemia reperfusion injury

KW - Lung transplantation

KW - Sprouty-related EVH1 (enabled/vasodilator-stimulated phosphoprotein homology 1)-domain-containing proteins (Spreds)

UR - http://www.scopus.com/inward/record.url?scp=85050208584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050208584&partnerID=8YFLogxK

U2 - 10.1007/s00595-018-1696-x

DO - 10.1007/s00595-018-1696-x

M3 - Article

C2 - 30022248

AN - SCOPUS:85050208584

JO - Japanese Journal of Surgery

JF - Japanese Journal of Surgery

SN - 0941-1291

ER -