Nrf2 and STAT3 Alleviates Ferroptosis-Mediated IIR-ALI by Regulating SLC7A11.
Nrf2 and STAT3 Alleviates Ferroptosis-Mediated IIR-ALI by Regulating SLC7A11.
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DOI：
10.1155/2020/5146982
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发表时间：
2020
影响因子：
--
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
Qiang Z;Dong H;Xia Y;Chai D;Hu R;Jiang H
急性肺损伤（ALI）在危重病研究领域得到了越来越多的关注，其病死率约为50%。核因子红细胞2相关因子2（Nrf 2）是细胞内氧化稳态的关键调节因子，也是一种抗氧化剂。已有报道Nrf 2相关的抗氧化应激与铁凋亡抑制密切相关。信号转导子和转录激活子3（STAT 3）响应于组织损伤而被激活成磷酸化STAT 3（pSTAT 3），并作为增强炎症反应的警告信号。本研究采用C57 BL/6小鼠建立肠缺血再灌注诱导的急性肺损伤（IIR-ALI）模型，探讨Nrf 2在IIR-ALI相关铁凋亡中的调控作用。与IIR-ALI组相比，尾静脉注射Fe（15 mg/kg）或ferrostatin-1（5 mg/kg）（分别为铁凋亡促进剂和抑制剂）可加重或减轻肺损伤和肺水肿。Nrf 2在IIR-ALI中增加，并促进STAT 3磷酸化以放大下游信号。采用MLE 12细胞建立体外氧糖剥夺再给氧（OGD-R）模型，模拟缺血/再灌注条件。用慢病毒转染细胞以增加或下调STAT 3的水平。我们发现Nrf 2和STAT 3通过调节SLC 7A 11在铁凋亡中发挥关键作用，从而改善与ALI相关的病理过程。
Acute lung injury (ALI) has gained increased attention in the field of critical illness research and is associated with a fatality rate of approximately 50%. Nuclear factor erythroid 2-related factor2 (Nrf2) is a key regulator of intracellular oxidation homeostasis and also functions as an antioxidant. It has been reported that Nrf2 associated antioxidant stress is closely related to ferroptosis inhibition. Signal transducer and activator of transcription 3 (STAT3) is activated into phosphorylated STAT3 (pSTAT3) in response to tissue damage and serves as a warning signal to enhance the inflammatory response. In this study, an intestinal ischemia/reperfusion-induced acute lung injury (IIR-ALI) model was established in C57BL/6 mice to investigate the role of Nrf2 in regulating IIR-ALI-associated ferroptosis. Compared with those in the IIR-ALI group, the injection of Fe (15 mg/kg) or ferrostatin-1 (5 mg/kg) (ferroptosis promoter and inhibitor, respectively) via the tail vein could aggravate or alleviate lung injury and pulmonary edema, respectively. Nrf2 was increased in IIR-ALI and promoted the phosphorylation of STAT3 to amplify downstream signals. An in vitro oxygen-glucose deprivation and reoxygenation (OGD-R) model was established in MLE12 cells to imitate the ischemia/reperfusion condition. The cells were transfected with lentiviruses to increase or downregulate the levels of STAT3. We found that Nrf2 and STAT3 played key roles in ferroptosis by regulating SLC7A11, which improved the pathological processes associated with ALI.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
影响因子：
3.7
作者：
Linher-Melville K;Nashed MG;Ungard RG;Haftchenary S;Rosa DA;Gunning PT;Singh G
通讯作者：
Singh G
影响因子：
2.5
作者：
Acosta, Stefan
通讯作者：
Acosta, Stefan
影响因子：
19.6
作者：
Linkermann, Andreas;Braesen, Jan H.;Krautwald, Stefan
通讯作者：
Krautwald, Stefan
DOI：
10.1073/pnas.1415518111
发表时间：
2014-11-25
影响因子：
11.1
作者：
Linkermann, Andreas;Skouta, Rachid;Krautwald, Stefan
通讯作者：
Krautwald, Stefan