Upregulated miR-200c is associated with downregulation of the functional receptor for severe acute respiratory syndrome coronavirus 2 ACE2 in individuals with obesity.
Upregulated miR-200c is associated with downregulation of the functional receptor for severe acute respiratory syndrome coronavirus 2 ACE2 in individuals with obesity.
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DOI：
10.1038/s41366-021-00984-2
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Katare R
中科院分区：
文献类型：
--
作者：
Bellae Papannarao J;Schwenke DO;Manning P;Katare R
肥胖是冠状病毒病2019(新冠肺炎)感染的风险因素，研究表明，肥胖患者进入新冠肺炎的患病率在30%到60%之间。我们确定了早期microRNAs(MiRNAs)的变化是否与血管紧张素转换酶2(ACE2)的调节失调有关，血管紧张素转换酶2是SARS冠状病毒2的特异性功能受体。ACE2是一种膜结合的酶，催化血管紧张素II转化为血管紧张素1-7，后者具有心脏保护和血管松弛作用。对循环中miRNAs的血浆样本的实时定量PCR分析显示，在其他健康的肥胖者中，miR-200c和miR-let-7b表达上调。这与肥胖者ACE2的显著下调有关，ACE2是两种miRNAs的直接靶标。相关分析表明，ACE2与两种miRNAs均呈显著负相关。研究表明，尽管是功能性受体，抑制/下调血管紧张素转换酶2并不能降低新冠肺炎感染的严重程度。相反，血管紧张素II在抑制血管紧张素转换酶2后升高可能会增加疾病的严重性。综上所述，我们的新结果证实，miR-200C上调可能会增加肥胖者对新冠肺炎的易感性。考虑到miRNA是最早的分子调节因子，循环中miR-200C的水平可能成为早期识别严重新冠肺炎高危人群的潜在生物标志物。
Obesity is a risk factor for coronavirus disease 2019 (COVID-19) infection, with studies demonstrating the prevalence of individuals with obesity admitted with COVID-19 ranging between 30 and 60%. We determined whether early changes in microRNAs (miRNAs) are associated with dysregulation of angiotensin-converting enzyme 2 (ACE2), the specific functional receptor for severe acute respiratory syndrome coronavirus 2. ACE2 is a membrane-bound enzyme that catalyzes the conversion of angiotensin II to angiotensin 1–7 the latter having cardioprotective and vasorelaxation effects. Quantitative real-time PCR analysis of plasma samples for circulating miRNAs showed upregulation of miR-200c and miR-let-7b in otherwise healthy individuals with obesity. This was associated with significant downregulation of ACE2, a direct target for both miRNAs, in individuals with obesity. Correlation analysis confirmed a significant negative correlation between ACE2 and both the miRNAs. Studies showed that despite being the functional receptor, inhibition/downregulation of ACE2 did not reduce the severity of COVID-19 infection. In contrast, increased angiotensin II following inhibition of ACE2 may increase the severity of the disease. Taken together, our novel results identify that upregulation of miR-200c may increase the susceptibility of individuals with obesity to COVID-19. Considering miRNA are the earliest molecular regulators, the level of circulating miR-200c could be a potential biomarker in the early identification of those at the risk of severe COVID-19.
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