Although a defective vitamin D pathway has been widely suspected to be associated in SARS-CoV-2 pathobiology, the status of the vitamin D pathway and vitamin D-modulated genes in lung cells of patients infected with SARS-CoV-2 remains unknown. To understand the significance of the vitamin D pathway in SARS-CoV-2 pathobiology, computational approaches were applied to transcriptomic datasets from bronchoalveolar lavage fluid (BALF) cells of such patients or healthy individuals. Levels of vitamin D receptor, retinoid X receptor, and CYP27A1 in BALF cells of patients infected with SARS-CoV-2 were found to be reduced. Additionally, 107 differentially expressed, predominantly downregulated genes modulated by vitamin D were identified in transcriptomic datasets from patient's cells. Further analysis of differentially expressed genes provided eight novel genes with a conserved motif with vitamin D-responsive elements, implying the role of both direct and indirect mechanisms of gene expression by the dysregulated vitamin D pathway in SARS-CoV-2-infected cells. Network analysis of differentially expressed vitamin D-modulated genes identified pathways in the immune system, NF-kB/cytokine signaling, and cell cycle regulation as top predicted pathways that might be affected in the cells of such patients. In brief, the results provided computational evidence to implicate a dysregulated vitamin D pathway in the pathobiology of SARS-CoV-2 infection.

中文翻译：

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SARS-CoV-2感染患者肺细胞中维生素D通路失调的证据

尽管人们普遍怀疑有缺陷的维生素D途径与SARS-CoV-2病理生物学有关，但是，感染SARS-CoV-2的患者肺细胞中维生素D途径和维生素D调节基因的状态仍然未知。为了了解维生素D途径在SARS-CoV-2病理生物学中的重要性，将计算方法应用于此类患者或健康个体的支气管肺泡灌洗液（BALF）细胞的转录组数据集。发现SARS-CoV-2感染患者的BALF细胞中维生素D受体，类维生素A X受体和CYP27A1的水平降低。此外，在患者细胞的转录组数据集中，鉴定了107种差异表达的，主要是由维生素D调节的下调基因。差异表达基因的进一步分析提供了八个新基因，具有带有维生素D反应元件的保守基序，这暗示了SARS-CoV-2感染细胞中维生素D途径失调直接和间接表达基因的作用。对差异表达的维生素D调节基因的网络分析确定了免疫系统中的途径，NF-kB /细胞因子信号传导和细胞周期调控是此类患者细胞中可能受影响的最主要的预测途径。简而言之，该结果提供了计算证据，暗示在SARS-CoV-2感染的病理生物学中维生素D通路失调。这暗示了在SARS-CoV-2感染的细胞中，维生素D途径失调直接或间接地影响了基因表达的机制。对差异表达的维生素D调节基因的网络分析确定了免疫系统中的途径，NF-kB /细胞因子信号传导和细胞周期调节，是此类患者细胞中可能受到影响的最主要的预测途径。简而言之，该结果提供了计算证据，暗示在SARS-CoV-2感染的病理生物学中维生素D通路失调。这暗示了在SARS-CoV-2感染的细胞中，维生素D途径失调直接或间接地影响了基因表达的机制。对差异表达的维生素D调节基因的网络分析确定了免疫系统中的途径，NF-kB /细胞因子信号传导和细胞周期调控是此类患者细胞中可能受影响的最主要的预测途径。简而言之，该结果提供了计算证据，暗示在SARS-CoV-2感染的病理生物学中维生素D通路失调。