WISP1 mediates lung injury following hepatic ischemia reperfusion dependent on TLR4 in mice
WISP1 mediates lung injury following hepatic ischemia reperfusion dependent on TLR4 in mice
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WISP1 依赖 TLR4 介导小鼠肝缺血再灌注后的肺损伤
DOI：
10.1186/s12890-018-0744-z
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发表时间：
2018-12-06
影响因子：
3.1
通讯作者：
Li, Quan
中科院分区：
文献类型：
--
作者：
Tong, Yao;Yu, Zhuang;Li, Quan
【摘要】 研究背景肝缺血再灌注损伤(IRI)是一种常见的病理现象,不仅会导致肝脏损伤,还会导致肺等远端器官损伤。再灌注后肝脏和远端器官损伤的发病机制中暗示了多种介质，例如氧化应激、Ca2+超载和中性粒细胞浸润。 WNT1 诱导信号通路蛋白 1 (WISP1) 是一种细胞外基质蛋白，与多种恶性疾病的发生有关。我们小组之前的工作已证明 WISP1 上调并有助于肝脏 IRI 中的促炎症级联反应。然而，WISP1在肝IRI后肺损伤发病机制中的作用仍不清楚。方法采用雄性C57BL/6小鼠检测WISP1在肝IRI后肺损伤发病机制中的表达和作用，探讨其介导肺损伤的潜在机制。结果发现WISP1在肝IRI后肺组织中表达上调。抗 WISP1 抗体治疗可通过改变细胞因子谱来改善肺损伤。 rWISP1通过过量产生促炎细胞因子和抑制抗炎细胞因子而加重肝IRI后的肺损伤。结论在本研究中，我们得出结论，WISP1通过TLR4途径导致肝IRI后的肺损伤。
BackgroundHepatic ischemia-reperfusion injury (IRI) is a common pathological phenomenon, which causes hepatic injury as well as remote organ injuries such as the lung. Several mediators, such as oxidative stress, Ca2+overload and neutrophil infiltration, have been implied in the pathogenesis of liver and remote organ injuries following reperfusion. WNT1 inducible signaling pathway protein 1 (WISP1) is an extracellular matrix protein that has been associated with the onset of several malignant diseases. Previous work in our group has demonstrated WISP1 is upregulated and contributes to proinflammatory cascades in hepatic IRI. However, the role of WISP1 in the pathogenesis of lung injury after hepatic IRI still remains unknown.MethodsMale C57BL/6 mice were used to examine the expression and role of WISP1 in the pathogenesis of lung injuries after hepatic IRI and explore its potential mechanisms in mediating lung injuries.ResultsWe found WISP1 was upregulated in lung tissues following hepatic IRI. Treatment with anti-WISP1 antibody ameliorated lung injuries with alteration of cytokine profiles. Administration with rWISP1 aggravated lung injuries following hepatic IRI through excessive production of proinflammatory cytokines and inhibition of anti-inflammatory cytokines.ConclusionsIn this study, we concluded that WISP1 contributed to lung injuries following hepatic IRI through TLR4 pathway.