Summary: Recently, a short, interferon-inducible isoform of Angiotensin-Converting Enzyme 2 (ACE2), dACE2 was identified. ACE2 is a SARS-Cov-2 receptor and changes in its renal expression have been linked to several human nephropathies. These changes were never analyzed in context of dACE2, as its expression was not investigated in the kidney. We used Human Primary Proximal Tubule (HPPT) cells to show genome-wide gene expression patterns after cytokine stimulation, with emphasis on the ACE2/dACE2 locus. Putative regulatory elements controlling dACE2 expression were identified using ChIP-seq and RNA-seq. qRT-PCR differentiating between ACE2 and dACE2 revealed 300- and 600-fold upregulation of dACE2 by IFNα and IFNβ, respectively, while full length ACE2 expression was almost unchanged. JAK inhibitor ruxolitinib ablated STAT1 and dACE2 expression after interferon treatment. Finally, with RNA-seq, we identified a set of genes, largely immune-related, induced by cytokine treatment. These gene expression profiles provide new insights into cytokine response of proximal tubule cells.

中文翻译：

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干扰素调节的遗传程序和JAK / STAT通路激活肾小管中短ACE2亚型的内含子启动子

摘要：最近，鉴定了血管紧张素转换酶2（ACE2）dACE2的短干扰素诱导亚型。ACE2是SARS-Cov-2受体，其肾脏表达的改变与几种人类肾病有关。从未在dACE2的背景下分析这些变化，因为尚未在肾脏中研究其表达。我们使用人类原发近端小管（HPPT）细胞显示细胞因子刺激后，重点是ACE2 / dACE2基因座的全基因组基因表达模式。使用ChIP-seq和RNA-seq鉴定了控制dACE2表达的假定调控元件。区分ACE2和dACE2的qRT-PCR表明，IFNα和IFNβ分别使dACE2上调300倍和600倍，而全长ACE2的表达几乎没有变化。干扰素治疗后，JAK抑制剂ruxolitinib消除了STAT1和dACE2的表达。最后，利用RNA-seq，我们确定了由细胞因子处理诱导的一组基因，这些基因在很大程度上与免疫相关。这些基因表达谱为近端小管细胞的细胞因子反应提供了新的见识。