Soluble epoxide hydrolase deficiency attenuates airway inflammation in COPD via IRE1α/JNK/AP-1 signaling pathway.
Soluble epoxide hydrolase deficiency attenuates airway inflammation in COPD via IRE1α/JNK/AP-1 signaling pathway.
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DOI：
10.1186/s12950-023-00361-y
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发表时间：
2023-11-01
影响因子：
5.1
通讯作者：
Yu, Ganggang
中科院分区：
文献类型：
--
作者：
Yu, Yue;Yang, Ailin;He, Xin;Wu, Bo;Wu, Yanjun;Li, Yunxiao;Nie, Shan;Xu, Bo;Wang, Haoyan;Yu, Ganggang
可溶性环氧化物水解酶（sEH）代谢抗炎环氧二十碳三烯酸，并严重影响慢性阻塞性肺疾病（COPD）的气道炎症。考虑到过度的内质网应激与COPD的早期发病有关。sEH和内质网应激在COPD发病机制中的作用尚不清楚。采用慢性阻塞性肺疾病（COPD）小鼠模型，观察sEH与内质网应激的关系。本研究以体外培养的人上皮细胞为研究对象，探讨sEH在香烟烟雾诱导的内质网应激中的调控机制。sEH缺乏通过减轻内质网应激反应有助于减少烟雾暴露后肺气肿的形成。sEH缺乏可有效逆转香烟烟雾提取物诱导的IRE 1 α和JNK磷酸化及AP-1核表达的上调，减轻炎症因子的分泌。内质网应激和IRE 1 α抑制剂治疗可下调香烟烟雾提取物诱导的sEH表达和炎症因子分泌。sEH可能通过IRE 1 α/JNK/AP-1途径减轻气道炎症反应和内质网应激，从而减轻长期吸烟所致的肺损伤，为COPD的防治提供新的药理学靶点。
Soluble Epoxide Hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids and critically affects airway inflammation in chronic obstructive pulmonary disease (COPD). Considering the excessive endoplasmic reticulum stress is associated with the earlier onset of COPD. The role of sEH and endoplasmic reticulum stress in the pathogenesis of COPD remains unknown. 16 weeks of cigarette-exposed mice were used to detect the relationship between sEH and endoplasmic reticulum stress in COPD. Human epithelial cells were used in vitro to determine the regulation mechanism of sEH in endoplasmic reticulum stress induced by cigarette smoke. sEH deficiency helps reduce emphysema formation after smoke exposure by alleviating endoplasmic reticulum stress response. sEH deficiency effectively reverses the upregulation of phosphorylation IRE1α and JNK and the nuclear expression of AP-1, alleviating the secretion of inflammatory factors induced by cigarette smoke extract. Furthermore, the treatment with endoplasmic reticulum stress and IRE1α inhibitor downregulated cigarette smoke extract-induced sEH expression and the secretion of inflammatory factors. sEH probably alleviates airway inflammatory response and endoplasmic reticulum stress via the IRE1α/JNK/AP-1 pathway, which might attenuate lung injury caused by long-term smoking and provide a new pharmacological target for preventing and treating COPD.
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DOI：
10.1073/pnas.2118818119
发表时间：
2022-03-01
影响因子：
11.1
作者：
Sun CP;Zhou JJ;Yu ZL;Huo XK;Zhang J;Morisseau C;Hammock BD;Ma XC
通讯作者：
Ma XC
通过破坏的顺序：与ER相关的蛋白质降解如何有助于细胞器稳态。
DOI：
10.15252/embj.2021109845
发表时间：
2022-03-15
期刊：
The EMBO journal
影响因子：
--
作者：
Christianson JC;Carvalho P
通讯作者：
Carvalho P
影响因子：
7.9
作者：
Lee, Jae-Won;Kim, Mun-Ock;Lee, Su Ui
通讯作者：
Lee, Su Ui
抑制可溶性环氧化物水解酶可减轻博舒替尼引起的血压升高
DOI：
10.1161/hypertensionaha.121.17548
发表时间：
2021-11
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Cui Z;Li B;Zhang Y;He J;Shi X;Wang H;Zhao Y;Yao L;Ai D;Zhang X;Zhu Y
通讯作者：
Zhu Y
DOI：
10.1084/jem.20200938
发表时间：
2021-08-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hisata S;Racanelli AC;Kermani P;Schreiner R;Houghton S;Palikuqi B;Kunar B;Zhou A;McConn K;Capili A;Redmond D;Nolan DJ;Ginsberg M;Ding BS;Martinez FJ;Scandura JM;Cloonan SM;Rafii S;Choi AMK
通讯作者：
Choi AMK