Upregulation of Matrix Metalloproteinase-9 Protects against Sepsis-Induced Acute Lung Injury via Promoting the Release of Soluble Receptor for Advanced Glycation End Products.
Upregulation of Matrix Metalloproteinase-9 Protects against Sepsis-Induced Acute Lung Injury via Promoting the Release of Soluble Receptor for Advanced Glycation End Products.
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基质金属蛋白酶 9 的上调可通过促进高级糖基化终产物可溶性受体的释放来预防脓毒症引起的急性肺损伤
DOI：
10.1155/2021/8889313
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发表时间：
2021
影响因子：
--
通讯作者：
Liu YJ
中科院分区：
文献类型：
--
作者：
Zhang H;Mao YF;Zhao Y;Xu DF;Wang Y;Xu CF;Dong WW;Zhu XY;Ding N;Jiang L;Liu YJ
基质金属蛋白酶- (MMP-) 9的失调与急性肺损伤（ALI）的发病机制有关。然而，MMP-9是改善还是恶化不同病因的急性肺损伤仍存在争议。晚期糖基化终产物受体（RAGE）在急性肺损伤的发病机制中起着关键作用。已知MMPs介导RAGE脱落和可溶性RAGE （sRAGE）的释放，可通过竞争性抑制RAGE配体与RAGE的结合而作为诱饵受体。因此，本研究旨在阐明MMP-9在小鼠盲肠结扎穿刺（CLP）模型中是否以及如何影响脓毒症诱导的急性肺损伤以及sRAGE的释放。对GEO小鼠脓毒症数据集GSE15379、GSE52474和GSE60088的分析显示，MMP-9的mRNA表达在脓毒症小鼠肺组织中显著上调。clp诱导小鼠脓毒症模型证实肺MMP-9 mRNA和蛋白表达升高。气管内注射MMP-9 siRNA导致肺MMP-9表达降低约60%。结果发现，肺中MMP-9的敲低显著增加败血症的死亡率和加重败血症相关的急性肺损伤。肺部MMP-9敲低也会降低sRAGE的释放，增强败血症诱导的RAGE/核因子-κB （NF-κB）信号通路的激活，同时加重败血症诱导的肺组织氧化应激和炎症。此外，重组sRAGE蛋白可抑制RAGE/NF-κB信号通路的激活，改善clp诱导的脓毒症小鼠的肺氧化应激、炎症和肺损伤。总之，我们的数据表明，mmp -9介导的RAGE释放通过sRAGE的诱饵受体活性抑制RAGE/NF-κB信号通路，从而限制败血症相关肺水肿、炎症、氧化应激和肺损伤的严重程度。mmp -9介导的sRAGE的产生可能作为一种自我限制的机制来控制和解决败血症期间肺部过度的炎症和氧化应激。
Dysregulation of matrix metalloproteinase- (MMP-) 9 is implicated in the pathogenesis of acute lung injury (ALI). However, it remains controversial whether MMP-9 improves or deteriorates acute lung injury of different etiologies. The receptor for advanced glycation end products (RAGE) plays a critical role in the pathogenesis of acute lung injury. MMPs are known to mediate RAGE shedding and release of soluble RAGE (sRAGE), which can act as a decoy receptor by competitively inhibiting the binding of RAGE ligands to RAGE. Therefore, this study is aimed at clarifying whether and how pulmonary knockdown of MMP-9 affected sepsis-induced acute lung injury as well as the release of sRAGE in a murine cecal ligation and puncture (CLP) model. The analysis of GEO mouse sepsis datasets GSE15379, GSE52474, and GSE60088 revealed that the mRNA expression of MMP-9 was significantly upregulated in septic mouse lung tissues. Elevation of pulmonary MMP-9 mRNA and protein expressions was confirmed in CLP-induced mouse sepsis model. Intratracheal injection of MMP-9 siRNA resulted in an approximately 60% decrease in pulmonary MMP-9 expression. It was found that pulmonary knockdown of MMP-9 significantly increased mortality of sepsis and exacerbated sepsis-associated acute lung injury. Pulmonary MMP-9 knockdown also decreased sRAGE release and enhanced sepsis-induced activation of the RAGE/nuclear factor-κB (NF-κB) signaling pathway, meanwhile aggravating sepsis-induced oxidative stress and inflammation in lung tissues. In addition, administration of recombinant sRAGE protein suppressed the activation of the RAGE/NF-κB signaling pathway and ameliorated pulmonary oxidative stress, inflammation, and lung injury in CLP-induced septic mice. In conclusion, our data indicate that MMP-9-mediated RAGE shedding limits the severity of sepsis-associated pulmonary edema, inflammation, oxidative stress, and lung injury by suppressing the RAGE/NF-κB signaling pathway via the decoy receptor activities of sRAGE. MMP-9-mediated sRAGE production may serve as a self-limiting mechanism to control and resolve excessive inflammation and oxidative stress in the lung during sepsis.
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影响因子：
5.7
作者：
Hegde, Akhil;Tamizhselvi, Ramasamy;Bhatia, Madhav
通讯作者：
Bhatia, Madhav
影响因子：
38.9
作者：
Jabaudon M;Blondonnet R;Pereira B;Cartin-Ceba R;Lichtenstern C;Mauri T;Determann RM;Drabek T;Hubmayr RD;Gajic O;Uhle F;Coppadoro A;Pesenti A;Schultz MJ;Ranieri MV;Brodska H;Mrozek S;Sapin V;Matthay MA;Constantin JM;Calfee CS
通讯作者：
Calfee CS
白藜芦醇对肺内皮屏障的保护涉及通过 Nrf2 依赖性机制抑制 HMGB1 释放和 HMGB1 诱导的线粒体氧化损伤
影响因子：
7.4
作者：
Dong, Wen-Wen;Liu, Yu-Jian;Jiang, Lai
通讯作者：
Jiang, Lai
影响因子：
4.6
作者：
Detzen, Laurent;Cheng, Bin;Lalla, Evanthia
通讯作者：
Lalla, Evanthia
DOI：
10.1097/shk.0000000000000386
发表时间：
2015-08
期刊：
Shock (Augusta, Ga.)
影响因子：
--
作者：
Hsu AT;Barrett CD;DeBusk GM;Ellson CD;Gautam S;Talmor DS;Gallagher DC;Yaffe MB
通讯作者：
Yaffe MB