Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19.
Ephrin-A1 and the sheddase ADAM12 are upregulated in COVID-19.
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DOI：
10.1016/j.heliyon.2021.e07200
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发表时间：
2021-06
期刊：
影响因子：
4
通讯作者：
Nikolov DB
中科院分区：
文献类型：
--
作者：
Mendoza R;Saha N;Momeni A;Gabutan E;Alawad M;Dehghani A;Diks J;Lin B;Wang D;Alshal M;Fyke W;Wang B;Himanen JP;Premsrirut P;Nikolov DB
全球已有350多万人死于新冠肺炎，但目前还没有有效的治疗方法。因此，重要的是要了解介导疾病进展的信号通路，以便为治疗开发确定新的分子靶点。在这里，我们报告了在纽约纽约州立大学布鲁克林下州医院接受治疗的新冠肺炎患者的血清肾上腺素A1和脱落酶ADAM12水平显著升高。已知ePhin-A1和ADAM12都参与炎症和调节内皮细胞通透性，从而为肺损伤提供了一条通道。在入院的第一周内，临床结果与血清中的肾上腺素A1和ADAM12水平相关。相比之下，只有一小部分患者的血清肿瘤坏死因子α水平升高，这些患者的脱落酶ADAM17水平也高度升高。这些数据表明，肾上腺素A1介导的炎症信号可能比肿瘤坏死因子α介导的炎症信号在新冠肺炎疾病进展中的作用更大。他们还支持这样的观点，在新冠肺炎炎症中，ADAM12释放ephin-A1，而ADAM17释放肿瘤坏死因子α。此外，结果表明，血清中细胞因子水平和活性的升高，如肿瘤坏死因子α和其他分泌性炎症分子，如EPhin-A1，不仅仅是由于过度表达，而且还因为释放它们进入血液循环的脱落酶上调。我们的结果确定eaffin-A1、ADAM12和eaffin-A1信号通路中的其他分子是治疗新冠肺炎炎症的潜在药理靶点。新冠肺炎，炎症，伊夫林，EPH受体，亚当蛋白酶。
More than 3.5 million people have died globally from COVID-19, yet an effective therapy is not available. It is, therefore, important to understand the signaling pathways that mediate disease progression in order to identify new molecular targets for therapeutic development. Here, we report that the blood serum levels of ephrin-A1 and the sheddase ADAM12 were significantly elevated in COVID-19 patients treated at SUNY Downstate Hospital of Brooklyn, New York. Both ephrin-A1 and ADAM12 are known to be involved in inflammation and regulate endothelial cell permeability, thus providing a gateway to lung injury. The clinical outcome correlated with the ephrin-A1 and ADAM12 serum levels during the first week of hospitalization. In contrast, the serum levels of TNFα were elevated in only a small subset of the patients, and these same patients also had highly elevated levels of the sheddase ADAM17. These data indicate that ephrin-A1-mediated inflammatory signaling may contribute to COVID-19 disease progression more so than TNFα-mediated inflammatory signaling. They also support the notion that, in COVID-19 inflammation, ADAM12 sheds ephrin-A1, while ADAM17 sheds TNFα. Furthermore, the results suggest that elevated serum levels and activity of cytokines, such as TNFα, and other secreted inflammatory molecules, such as ephrin-A1, are not simply due to overexpression, but also to upregulation of sheddases that release them into the blood circulation. Our results identify ephrin-A1, ADAM12, and other molecules in the ephrin-A1 signaling pathway as potential pharmacological targets for treating COVID-19 inflammation. COVID-19, Inflammation, Ephrin, Eph receptors, ADAM proteases.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
4.8
作者：
Cheng, N;Chen, J
通讯作者：
Chen, J
影响因子：
20.3
作者：
Aasheim, HC;Delabie, J;Finne, EF
通讯作者：
Finne, EF
影响因子：
3.4
作者：
Fabes, Jez;Anderson, Patrick;Bolsover, Stephen
通讯作者：
Bolsover, Stephen
DOI：
10.1152/ajplung.00118.2009
发表时间：
2009-11-01
影响因子：
4.9
作者：
Cercone, Melissa A.;Schroeder, William;Carpenter, Todd C.
通讯作者：
Carpenter, Todd C.