Skip to main content
Erschienen in: Surgery Today 12/2018

18.07.2018 | Original Article

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

verfasst von: Masanori Okada, Masaomi Yamane, Sumiharu Yamamoto, Shinji Otani, Kentaroh Miyoshi, Seiichiro Sugimoto, Akihiro Matsukawa, Shinichi Toyooka, Takahiro Oto, Shinichiro Miyoshi

Erschienen in: Surgery Today | Ausgabe 12/2018

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia–reperfusion-induced lung injury. Am J Respir Crit Care Med. 2003;167(4):490–511.CrossRef de Perrot M, Liu M, Waddell TK, Keshavjee S. Ischemia–reperfusion-induced lung injury. Am J Respir Crit Care Med. 2003;167(4):490–511.CrossRef
2.
Zurück zum Zitat den Hengst WA, Gielis JF, Lin JY, Van Schil PE, De Windt LJ, Moens AL. Lung ischemia–reperfusion injury: a molecular and clinical view on a complex pathophysiological process. Am J Physiol Heart Circ Physiol. 2010;299(5):H1283-99. den Hengst WA, Gielis JF, Lin JY, Van Schil PE, De Windt LJ, Moens AL. Lung ischemia–reperfusion injury: a molecular and clinical view on a complex pathophysiological process. Am J Physiol Heart Circ Physiol. 2010;299(5):H1283-99.
3.
Zurück zum Zitat Carden DL, Granger DN. Pathophysiology of ischaemia–reperfusion injury. J Pathol. 2000;190:255–66.CrossRef Carden DL, Granger DN. Pathophysiology of ischaemia–reperfusion injury. J Pathol. 2000;190:255–66.CrossRef
4.
Zurück zum Zitat Ross SD, Tribble CG, Gaughen JRJ, Shockey KS, Parrino PE, Kron IL. Reduced neutrophil infiltration protects against lung reperfusion injury after transplantation. Ann Thorac Surg. 1999;67:1428–34.CrossRef Ross SD, Tribble CG, Gaughen JRJ, Shockey KS, Parrino PE, Kron IL. Reduced neutrophil infiltration protects against lung reperfusion injury after transplantation. Ann Thorac Surg. 1999;67:1428–34.CrossRef
5.
Zurück zum Zitat Cuzzocrea S, Mazzon E, Costantino G, Serraino I, De Sarro A, Caputi AP. Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury. Cardiovasc Res. 2000;47:537–48.CrossRef Cuzzocrea S, Mazzon E, Costantino G, Serraino I, De Sarro A, Caputi AP. Effects of n-acetylcysteine in a rat model of ischemia and reperfusion injury. Cardiovasc Res. 2000;47:537–48.CrossRef
6.
Zurück zum Zitat Millar TM, Phan V, Tibbles LA. ROS generation in endothelial hypoxia and reoxygenation stimulates MAP kinase signaling and kinase-dependent neutrophil recruitment. Free Radic Biol Med. 2007;42(8):1165–77.CrossRef Millar TM, Phan V, Tibbles LA. ROS generation in endothelial hypoxia and reoxygenation stimulates MAP kinase signaling and kinase-dependent neutrophil recruitment. Free Radic Biol Med. 2007;42(8):1165–77.CrossRef
7.
Zurück zum Zitat Sayah DM, Mallavia B, Liu F, Ortiz-Muñoz G, Caudrillier A, DerHovanessian A, et al. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2015;191(4):455–63.CrossRef Sayah DM, Mallavia B, Liu F, Ortiz-Muñoz G, Caudrillier A, DerHovanessian A, et al. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med. 2015;191(4):455–63.CrossRef
8.
Zurück zum Zitat Yamamoto S, Yamane M, Yoshida O, Waki N, Okazaki M, Matsukawa A, et al. Early growth response-1 plays an important role in ischemia–reperfusion injury in lung transplants by regulating polymorphonuclear neutrophil infiltration. Transplantation. 2015;99:2285–93.CrossRef Yamamoto S, Yamane M, Yoshida O, Waki N, Okazaki M, Matsukawa A, et al. Early growth response-1 plays an important role in ischemia–reperfusion injury in lung transplants by regulating polymorphonuclear neutrophil infiltration. Transplantation. 2015;99:2285–93.CrossRef
9.
Zurück zum Zitat Takano M, Meneshian A, Sheikh E, Yamakawa Y, Wilkins KB, Hopkins EA, et al. Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation. Am J Physiol Heart Circ Physiol. 2002;283(5):H2054-61.CrossRef Takano M, Meneshian A, Sheikh E, Yamakawa Y, Wilkins KB, Hopkins EA, et al. Rapid upregulation of endothelial P-selectin expression via reactive oxygen species generation. Am J Physiol Heart Circ Physiol. 2002;283(5):H2054-61.CrossRef
10.
Zurück zum Zitat Seger R, Krebs EG. The MAPK signaling cascade. FASEB J. 1995;9:726–35.CrossRef Seger R, Krebs EG. The MAPK signaling cascade. FASEB J. 1995;9:726–35.CrossRef
11.
Zurück zum Zitat Strniskova M, Barancik M, Ravingerova T. Mitogen-activated protein kinases and their role in regulation of cellular processes. Gen Physiol Biophys. 2002;21(3):231–55.PubMed Strniskova M, Barancik M, Ravingerova T. Mitogen-activated protein kinases and their role in regulation of cellular processes. Gen Physiol Biophys. 2002;21(3):231–55.PubMed
12.
Zurück zum Zitat Junttila MR, Li SP, Westermarck J. Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. FASEB J. 2008;22(4):954–65.CrossRef Junttila MR, Li SP, Westermarck J. Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival. FASEB J. 2008;22(4):954–65.CrossRef
13.
Zurück zum Zitat Ishii M, Suzuki Y, Takeshita K, Miyao N, Kudo H, Hiraoka R, et al. Inhibition of c-Jun NH2-terminal kinase activity improves ischemia/reperfusion injury in rat lungs. J Immunol. 2004;172(4):2569–77.CrossRef Ishii M, Suzuki Y, Takeshita K, Miyao N, Kudo H, Hiraoka R, et al. Inhibition of c-Jun NH2-terminal kinase activity improves ischemia/reperfusion injury in rat lungs. J Immunol. 2004;172(4):2569–77.CrossRef
14.
Zurück zum Zitat Kawashima Y, Takeyoshi I, Otani Y, Koibuchi Y, Yoshinari D, Koyama T, et al. FR167653 attenuates ischemia and reperfusion injury of the rat lung with suppressing p38 mitogen-activated protein kinase. J Heart Lung Transplant. 2001;20:568–74.CrossRef Kawashima Y, Takeyoshi I, Otani Y, Koibuchi Y, Yoshinari D, Koyama T, et al. FR167653 attenuates ischemia and reperfusion injury of the rat lung with suppressing p38 mitogen-activated protein kinase. J Heart Lung Transplant. 2001;20:568–74.CrossRef
15.
Zurück zum Zitat Zhang X, Shan P, Otterbein LE, Alam J, Flavell RA, Davis RJ, et al. Carbon monoxide inhibition of apoptosis during ischemia–reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J Biol Chem. 2003;278(2):1248–58.CrossRef Zhang X, Shan P, Otterbein LE, Alam J, Flavell RA, Davis RJ, et al. Carbon monoxide inhibition of apoptosis during ischemia–reperfusion lung injury is dependent on the p38 mitogen-activated protein kinase pathway and involves caspase 3. J Biol Chem. 2003;278(2):1248–58.CrossRef
16.
Zurück zum Zitat Itakura J, Sato M, Ito T, Mino M, Fushimi S, Takahashi S, et al. Spred2-deficiecy protects mice from polymicrobial septic peritonitis by enhancing inflammation and bacterial clearance. Sci Rep. 2017;7(1):12833.CrossRef Itakura J, Sato M, Ito T, Mino M, Fushimi S, Takahashi S, et al. Spred2-deficiecy protects mice from polymicrobial septic peritonitis by enhancing inflammation and bacterial clearance. Sci Rep. 2017;7(1):12833.CrossRef
17.
Zurück zum Zitat Lu Z, Xu S. ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life. 2006;58(11):621–31.CrossRef Lu Z, Xu S. ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life. 2006;58(11):621–31.CrossRef
18.
Zurück zum Zitat Wada T, Penninger JM. Mitogen-activated protein kinases in apoptosis regulation. Oncogene. 2004;23(16):2838–49.CrossRef Wada T, Penninger JM. Mitogen-activated protein kinases in apoptosis regulation. Oncogene. 2004;23(16):2838–49.CrossRef
19.
Zurück zum Zitat Kwon DS, Kwon CH, Kim JH, Woo JS, Jung JS, Kim YK. Signal transduction of MEK/ERK and PI3K/Akt activation by hypoxia/reoxygenation in renal epithelial cells. Eur J Cell Biol. 2006;85(11):1189–99.CrossRef Kwon DS, Kwon CH, Kim JH, Woo JS, Jung JS, Kim YK. Signal transduction of MEK/ERK and PI3K/Akt activation by hypoxia/reoxygenation in renal epithelial cells. Eur J Cell Biol. 2006;85(11):1189–99.CrossRef
20.
Zurück zum Zitat Park KM, Chen A, Bonventre JV. Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem. 2001;276(15):11870–76.CrossRef Park KM, Chen A, Bonventre JV. Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment. J Biol Chem. 2001;276(15):11870–76.CrossRef
21.
Zurück zum Zitat Kaizu T, Ikeda A, Nakao A, Tsung A, Toyokawa H, Ueki S, et al. Protection of transplant-induced hepatic ischemia/reperfusion injury with carbon monoxide via MEK/ERK1/2 pathway downregulation. Am J Physiol Gastrointest Liver Physiol. 2008;294(1):G236-44.CrossRef Kaizu T, Ikeda A, Nakao A, Tsung A, Toyokawa H, Ueki S, et al. Protection of transplant-induced hepatic ischemia/reperfusion injury with carbon monoxide via MEK/ERK1/2 pathway downregulation. Am J Physiol Gastrointest Liver Physiol. 2008;294(1):G236-44.CrossRef
22.
Zurück zum Zitat Naito Z, Kubo M, Xu G, Nishigaki R, Yokoyama M, Yamada N, et al. Immunohistochemical localization of mitogen-activated protein kinase (MAPK) family and morphological changes in rat heart after ischemia–reperfusion injury. Med Electron Microsc. 2000;33:74–81.CrossRef Naito Z, Kubo M, Xu G, Nishigaki R, Yokoyama M, Yamada N, et al. Immunohistochemical localization of mitogen-activated protein kinase (MAPK) family and morphological changes in rat heart after ischemia–reperfusion injury. Med Electron Microsc. 2000;33:74–81.CrossRef
23.
Zurück zum Zitat Sakiyama S, Hamilton J, Han B, Jiao Y, Shen-Tu G, de Perrot M, et al. Activation of mitogen-activated protein kinases during human lung transplantation. J Heart Lung Transplant. 2005;24(12):2079–85.CrossRef Sakiyama S, Hamilton J, Han B, Jiao Y, Shen-Tu G, de Perrot M, et al. Activation of mitogen-activated protein kinases during human lung transplantation. J Heart Lung Transplant. 2005;24(12):2079–85.CrossRef
24.
Zurück zum Zitat Wakioka T, Sasaki A, Kato R, Shouda T, Matsumoto A, Miyoshi K, et al. Spred is a sprouty-related suppressor of Ras signalling. Nature. 2001;412(6847):647–51.CrossRef Wakioka T, Sasaki A, Kato R, Shouda T, Matsumoto A, Miyoshi K, et al. Spred is a sprouty-related suppressor of Ras signalling. Nature. 2001;412(6847):647–51.CrossRef
25.
Zurück zum Zitat Yoshimura A. Regulation of cytokine signaling by the SOCS and Spred family proteins. Keio J Med. 2009;58(2):73–83.CrossRef Yoshimura A. Regulation of cytokine signaling by the SOCS and Spred family proteins. Keio J Med. 2009;58(2):73–83.CrossRef
26.
Zurück zum Zitat Nobuhisa I, Kato R, Inoue H, Takizawa M, Okita K, Yoshimura A, et al. Spred-2 suppresses aorta-gonad-mesonephros hematopoiesis by inhibiting MAP kinase activation. J Exp Med. 2004;199(5):737–42.CrossRef Nobuhisa I, Kato R, Inoue H, Takizawa M, Okita K, Yoshimura A, et al. Spred-2 suppresses aorta-gonad-mesonephros hematopoiesis by inhibiting MAP kinase activation. J Exp Med. 2004;199(5):737–42.CrossRef
27.
Zurück zum Zitat Taniguchi K, Kohno R, Ayada T, Kato R, Ichiyama K, Morisada T, et al. Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling. Mol Cell Biol. 2007;27(12):4541–50.CrossRef Taniguchi K, Kohno R, Ayada T, Kato R, Ichiyama K, Morisada T, et al. Spreds are essential for embryonic lymphangiogenesis by regulating vascular endothelial growth factor receptor 3 signaling. Mol Cell Biol. 2007;27(12):4541–50.CrossRef
28.
Zurück zum Zitat Xu Y, Ito T, Fushimi S, Takahashi S, Itakura J, Kimura R, et al. Spred-2 deficiency exacerbates lipopolysaccharide-induced acute lung inflammation in mice. PLoS One. 2014;9(9):e108914.CrossRef Xu Y, Ito T, Fushimi S, Takahashi S, Itakura J, Kimura R, et al. Spred-2 deficiency exacerbates lipopolysaccharide-induced acute lung inflammation in mice. PLoS One. 2014;9(9):e108914.CrossRef
29.
Zurück zum Zitat Zanotti G, Casiraghi M, Abano JB, Tatreau JR, Sevala M, Berlin H, et al. Novel critical role of Toll-like receptor 4 in lung ischemia–reperfusion injury and edema. Am J Physiol Lung Cell Mol Physiol. 2009;297(1):L52–63.CrossRef Zanotti G, Casiraghi M, Abano JB, Tatreau JR, Sevala M, Berlin H, et al. Novel critical role of Toll-like receptor 4 in lung ischemia–reperfusion injury and edema. Am J Physiol Lung Cell Mol Physiol. 2009;297(1):L52–63.CrossRef
30.
Zurück zum Zitat Li SP, Junttila MR, Han J, Kähäri VM, Westermarck J. p38 Mitogen-activated protein kinase pathway suppresses cell survival by inducing dephosphorylation of mitogen-activated protein/extracellular signal-regulated kinase kinase1,2. Cancer Res. 2003;63(13):3473–7.PubMed Li SP, Junttila MR, Han J, Kähäri VM, Westermarck J. p38 Mitogen-activated protein kinase pathway suppresses cell survival by inducing dephosphorylation of mitogen-activated protein/extracellular signal-regulated kinase kinase1,2. Cancer Res. 2003;63(13):3473–7.PubMed
31.
Zurück zum Zitat Ban K, Peng Z, Kozar RA. Inhibition of ERK1/2 worsens intestinal ischemia/reperfusion injury. PLoS One. 2013;8(9):e76790.CrossRef Ban K, Peng Z, Kozar RA. Inhibition of ERK1/2 worsens intestinal ischemia/reperfusion injury. PLoS One. 2013;8(9):e76790.CrossRef
32.
Zurück zum Zitat Liu FC, Chuang YH, Tsai YF, Yu HP. Role of neutrophil extracellular traps following injury. Shock. 2014;41(6):491–8.CrossRef Liu FC, Chuang YH, Tsai YF, Yu HP. Role of neutrophil extracellular traps following injury. Shock. 2014;41(6):491–8.CrossRef
Metadaten
Titel
SPRED2 deficiency may lead to lung ischemia–reperfusion injury via ERK1/2 signaling pathway activation
verfasst von
Masanori Okada
Masaomi Yamane
Sumiharu Yamamoto
Shinji Otani
Kentaroh Miyoshi
Seiichiro Sugimoto
Akihiro Matsukawa
Shinichi Toyooka
Takahiro Oto
Shinichiro Miyoshi
Publikationsdatum
18.07.2018
Verlag
Springer Singapore
Erschienen in
Surgery Today / Ausgabe 12/2018
Print ISSN: 0941-1291
Elektronische ISSN: 1436-2813
DOI
https://doi.org/10.1007/s00595-018-1696-x

Weitere Artikel der Ausgabe 12/2018

Surgery Today 12/2018 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

CME: 2 Punkte

Prof. Dr. med. Gregor Antoniadis Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

CME: 2 Punkte

Dr. med. Benjamin Meyknecht, PD Dr. med. Oliver Pieske Das Webinar S2e-Leitlinie „Distale Radiusfraktur“ beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

CME: 2 Punkte

Dr. med. Mihailo Andric
Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.