Activation of the SARS-CoV-2 Receptor Ace2 through JAK/STAT-Dependent Enhancers during Pregnancy
Activation of the SARS-CoV-2 Receptor Ace2 through JAK/STAT-Dependent Enhancers during Pregnancy
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DOI：
10.1016/j.celrep.2020.108199
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发表时间：
2020-09-29
期刊：
影响因子：
8.8
通讯作者：
Lee, Hye Kyung
中科院分区：
文献类型：
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作者：
Hennighausen, Lothar;Lee, Hye Kyung
ACE 2结合冠状病毒SARS-CoV-2并促进其进入细胞。干扰素激活肺细胞中ACE 2的表达，表明细胞因子在SARS-CoV-2靶细胞中的关键作用。在至少7项研究中，在母乳中检测到病毒RNA，这提高了ACE 2在哺乳期乳腺组织中表达的可能性。在这里，我们表明，Ace 2在小鼠乳腺组织中的表达诱导在怀孕和哺乳期间，这与内含子增强子的激活相一致。这些增强子被催乳素激活的转录因子STAT 5和其他调节因子（包括RNA聚合酶II）占据。Stat 5a的缺失导致增强子的退役和Ace 2 mRNA的83%的减少。我们还表明，Ace 2的表达增加哺乳期间在肺，但不是在肾脏和肠道。JAK/STAT组分存在于一系列SARS-CoV-2靶细胞中，这开启了细胞因子促进病毒载量和肺外病理生理学的可能性。
ACE2 binds the coronavirus SARS-CoV-2 and facilitates its cellular entry. Interferons activate ACE2 expression in pneumocytes, suggesting a critical role of cytokines in SARS-CoV-2 target cells. Viral RNA was detected in breast milk in at least seven studies, raising the possibility that ACE2 is expressed in mammary tissue during lactation. Here, we show that Ace2 expression in mouse mammary tissue is induced during pregnancy and lactation, which coincides with the activation of intronic enhancers. These enhancers are occupied by the prolactin-activated transcription factor STAT5 and additional regulatory factors, including RNA polymerase II. Deletion of Stat5a results in decommissioning of the enhancers and an 83% reduction of Ace2 mRNA. We also demonstrate that Ace2 expression increases during lactation in lung, but not in kidney and intestine. JAK/STAT components are present in a range of SARS-CoV-2 target cells, opening the possibility that cytokines contribute to the viral load and extrapulmonary pathophysiology.