当前位置: X-MOL 学术Transpl. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Negative impact of recipient SPRED2 deficiency on transplanted lung in a mouse model.
Transplant Immunology ( IF 1.6 ) Pub Date : 2019-08-22 , DOI: 10.1016/j.trim.2019.101242
Kohei Hashimoto 1 , Masaomi Yamane 1 , Seiichiro Sugimoto 1 , Yutaka Hirano 1 , Takeshi Kurosaki 2 , Shinji Otani 2 , Kentaroh Miyoshi 1 , Toshiaki Ohara 3 , Mikio Okazaki 1 , Teizo Yoshimura 3 , Takahiro Oto 2 , Akihiro Matsukawa 3 , Shinichi Toyooka 1
Affiliation  

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.



中文翻译:

受体SPRED2缺乏对小鼠模型中移植肺的负面影响。

肺移植后的缺血再灌注损伤(IRI)主要导致原发性移植物功能障碍的发展。含Sprouty相关EVH1域的蛋白家族(SPRED)抑制有丝分裂原激活的蛋白激酶/细胞外信号调节激酶(MAPK / ERK)途径。我们的研究旨在检查SPRED2在接受原位肺移植的小鼠IRI中的作用。在野生型C57BL / 6 J(WT)小鼠和Spred2基因敲除(Spred2-/-)小鼠中,在野生型C57BL / 6 J背景下进行了同种小鼠肺移植。再灌注后四小时,进行血气分析,并处死肺移植物并进行分析。通过使用动脉血氧分压测量和使用肺损伤评分的组织学评估,我们发现移植于Spred2 -/-受体,表现为气道上皮细胞损伤加剧,间质性水肿伴出血和中性粒细胞浸润。移植物内ERK1 /在促炎细胞因子和趋化因子2的活化和表达水平SPRED2 - / -收件人均较WT收件人更高。SPRED2在保护肺移植受者的IRI中起着重要的作用。我们建议在移植受者中抑制MAPK / ERK途径活性的集中治疗可能是预防肺IRI的潜在治疗选择。

更新日期:2019-08-22
down
wechat
bug