SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway.

SARS-CoV-2 attenuates corticosteroid sensitivity by suppressing DUSP1 expression and activating p38 MAPK pathway.
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SARS-CoV-2通过抑制DUSP 1表达和激活p38 MAPK途径减弱皮质类固醇敏感性。

DOI:
10.1016/j.ejphar.2021.174374
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发表时间:
2021-10-05
影响因子:
5
通讯作者:
Halwani R
Halwani R
中科院分区:
医学2区
文献类型:
--
作者:
Saheb Sharif-Askari F;Saheb Sharif-Askari N;Goel S;Hafezi S;Assiri R;Al-Muhsen S;Hamid Q;Halwani R

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皮质类固醇的疗效及其在治疗SARS-CoV-2感染方面的使用存在争议。在本研究中,利用SARS-CoV-2感染的肺组织和鼻咽拭子的数据集以及体外实验,我们发现SARS-CoV-2感染显著下调了DUSP1的表达。DUSP1的这种下调可能是SARS-CoV-2感染中MAPK通路激活增强和类固醇耐药的调节机制。此外,非标记性新冠肺炎药物氯喹能够诱导DUSP1并减弱MAPK通路;有望提高对类固醇治疗的敏感性。然而,还需要进一步的机制研究来证实这一效应。
The efficacy of corticosteroids and its use for the treatment of SARS-CoV-2 infections is controversial. In this study, using data sets of SARS-CoV-2 infected lung tissues and nasopharyngeal swabs, as well as in vitro experiments, we show that SARS-CoV-2 infection significantly downregulates DUSP1 expression. This downregulation of DUSP1 could be the mechanism regulating the enhanced activation of MAPK pathway as well as the reported steroid resistance in SARS-CoV-2 infection. Moreover, chloroquine, an off labeled COVID-19 drug is able to induce DUSP1 and attenuate MAPK pathway; and is expected to improve sensitivity to steroid treatment. However, further mechanistic studies are required to confirm this effect.
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