ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development.
ER stress mediates Angiotensin II-augmented innate immunity memory and facilitates distinct susceptibilities of thoracic from abdominal aorta to aneurysm development.
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DOI：
10.3389/fimmu.2023.1268916
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发表时间：
2023
影响因子：
7.3
通讯作者：
Yang, Xiaofeng
中科院分区：
文献类型：
--
作者：
Lu, Yifan;Sun, Yu;Saaoud, Fatma;Shao, Ying;Xu, Keman;Jiang, Xiaohua;Wu, Sheng;Yu, Jun;Snyder, Nathaniel W.;Yang, Ling;Shi, Xinghua Mindy;Zhao, Huaqing;Wang, Hong;Yang, Xiaofeng
为了确定内质网应激和训练免疫的作用，我们对血管紧张素II（Ang II）-HFD-ApoE-KO动脉瘤模型的胸主动脉（TA）和腹主动脉（AA）进行了转录组分析，发现：1）Ang II绕过HFD诱导的代谢重编程，在AA中诱导的炎症比TA更强; 2）Ang II和HFD上调AA与TA中的890个基因，并诱导细胞因子信号传导; 3）Ang II AA和TA上调73种和68种细胞因子，scRNA-Seq分别鉴定了巨噬细胞和免疫细胞的标志物、细胞死亡调节因子; Ang II-AA和TA可上调神经元、胶质细胞和鳞状上皮细胞的转分化标志物，而Ang II-AA对IL-1β和caspase-4介导的细胞凋亡信号的上调作用强于TA; 4）AAA患者中的六个上调转录组，Ang II AA，Ang II TA，另外的动脉瘤模型，PPE-AAA和BAPN-Ang II-AAA，与10个新的ER应激基因组列表部分重叠，包括ER应激调节因子ATF 6，PERK和IRE 1的3个相互作用蛋白列表，HPA ER定位基因，KEGG信号基因，XBP 1转录靶点，ATF 4（PERK）靶点，ATF 6靶点分别是毒胡萝卜素ER应激基因、衣霉素-ER应激基因; 5）Ang II-AA和TA上调ROS调节因子、MitoCarta基因、训练免疫基因和糖酵解基因; 6）基因KO转录组表明ATF 6和PERK在促进AAA和训练免疫中比IRE 1发挥更重要的作用，而抗氧化剂NRF 2抑制它们。我们前所未有的ER-聚焦转录组学分析提供了关于ER作为免疫细胞器在感知各种DAMP和启动ER应激中的作用的新见解，所述ER应激触发Ang II加速训练的免疫力，并使胸部和腹部肿瘤对疾病的易感性不同。
To determine the roles of endoplasmic reticulum (ER) stress and trained immunity, we performed transcriptome analyses on the thoracic aorta (TA) and abdominal aorta (AA) from the angiotensin II (Ang II)-HFD-ApoE-KO aneurysm model and made significant findings: 1) Ang II bypassed HFD-induced metabolic reprogramming and induced stronger inflammation in AA than in TA; 2) Ang II and HFD upregulated 890 genes in AA versus TA and induced cytokine signaling; 3) Ang II AA and TA upregulated 73 and 68 cytokines, scRNA-Seq identified markers of macrophages and immune cells, cell death regulators, respectively; transdifferentiation markers of neuron, glial, and squamous epithelial cells were upregulated by Ang II-AA and TA; and pyroptosis signaling with IL-1β and caspase-4 were more upregulated in Ang II-AA than in TA; 4) Six upregulated transcriptomes in patients with AAA, Ang II AA, Ang II TA, additional aneurysm models, PPE-AAA and BAPN-Ang II-AAA, were partially overlapped with 10 lists of new ER stress gene sets including 3 interaction protein lists of ER stress regulators ATF6, PERK, and IRE1, HPA ER localization genes, KEGG signal genes, XBP1 transcription targets, ATF4 (PERK) targets, ATF6 targets, thapsigargin ER stress genes, tunicamycin-ER stress genes, respectively; 5) Ang II-AA and TA upregulated ROS regulators, MitoCarta genes, trained immunity genes, and glycolysis genes; and 6) Gene KO transcriptomes indicated that ATF6 and PERK played more significant roles than IRE1 in promoting AAA and trained immunity whereas antioxidant NRF2 inhibited them. Our unprecedented ER-focused transcriptomic analyses have provided novel insights on the roles of ER as an immune organelle in sensing various DAMPs and initiating ER stress that triggers Ang II-accelerated trained immunity and differs susceptibilities of thoracic and abdominal aortas to diseases.
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DOI：
10.1126/science.abl5197
发表时间：
2022-05-13
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Domínguez Conde C;Xu C;Jarvis LB;Rainbow DB;Wells SB;Gomes T;Howlett SK;Suchanek O;Polanski K;King HW;Mamanova L;Huang N;Szabo PA;Richardson L;Bolt L;Fasouli ES;Mahbubani KT;Prete M;Tuck L;Richoz N;Tuong ZK;Campos L;Mousa HS;Needham EJ;Pritchard S;Li T;Elmentaite R;Park J;Rahmani E;Chen D;Menon DK;Bayraktar OA;James LK;Meyer KB;Yosef N;Clatworthy MR;Sims PA;Farber DL;Saeb-Parsy K;Jones JL;Teichmann SA
通讯作者：
Teichmann SA
影响因子：
4.1
作者：
Drummer CIV;Saaoud F;Sun Y;Atar D;Xu K;Lu Y;Shao Y;Johnson C;Liu L;Shen H;Jhala NC;Jiang X;Wang H;Yang X
通讯作者：
Yang X
影响因子：
5.6
作者：
Dong, Charlotte Xue;Malecki, Cassandra;Robertson, Elizabeth;Hambly, Brett;Jeremy, Richmond
通讯作者：
Jeremy, Richmond
影响因子：
39.3
作者：
Erbel, Raimund;Aboyans, Victor;Vrints, Christiaan J. M.
通讯作者：
Vrints, Christiaan J. M.
影响因子：
3.9
作者：
Bellini, C.;Bersi, M. R.;Humphrey, J. D.
通讯作者：
Humphrey, J. D.