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 language | English |
|---|---|
| Journal | Surgery Today |
| DOIs | |
| Publication status | Accepted/In press - Jan 1 2018 |
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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
SPRED2 deficiency may lead to lung ischemia–reperfusion injury via ERK1/2 signaling pathway activation. / Okada, Masanori; Yamane, Masaomi; Yamamoto, Sumiharu; Otani, Shinji; Miyoshi, Kentaroh; Sugimoto, Seiichiro; Matsukawa, Akihiro; Toyooka, Shinichi; Oto, Takahiro; Miyoshi, Shinichiro.
In: Surgery Today, 01.01.2018.Research output: Contribution to journal › Article
}
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 -