Doxycycline Changes the Transcriptome Profile of mIMCD3 Renal Epithelial Cells.
Doxycycline Changes the Transcriptome Profile of mIMCD3 Renal Epithelial Cells.
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DOI：
10.3389/fphys.2021.771691
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发表时间：
2021
影响因子：
4
通讯作者：
Welling PA
中科院分区：
文献类型：
--
作者：
Jung HJ;Coleman R;Woodward OM;Welling PA
四环素诱导基因表达系统已成功用于研究体内和体外肾上皮模型的基因功能，但常见诱导剂多西环素 (DOX) 对基因表达的影响尚未得到充分认识。在这里，我们评估了 DOX 对广泛使用的肾上皮细胞模型 mIMCD3 细胞转录组的影响，以建立参考。在不存在和存在 DOX 的情况下（3 或 6 天），细胞在可渗透过滤器支撑物上生长，并使用 RNA-Seq 评估全基因组转录组谱。我们发现 DOX 显着改变了转录组图谱，在 3 天时改变了 1,549 个转录本的丰度，在 6 天时改变了 2,643 个转录本的丰度。治疗 3 天内，DOX 显着降低了与细胞增殖和分化相关的多种信号通路（ERK、cAMP 和 Notch）的表达。随后，在用 DOX 处理 6 天的细胞中，与细胞周期进程相关的基因被下调，参与细胞免疫反应过程的基因以及多种细胞因子和趋化因子也被下调，这与编码细胞增殖标记物的基因的显着抑制相关。这些结果为肾上皮细胞对 DOX 的反应提供了新的见解，并为 DOX 介导的基因表达系统建立了资源。
Tetracycline-inducible gene expression systems have been used successfully to study gene function in vivo and in vitro renal epithelial models but the effects of the common inducing agent, doxycycline (DOX), on gene expression are not well appreciated. Here, we evaluated the DOX effects on the transcriptome of a widely used renal epithelial cell model, mIMCD3 cells, to establish a reference. Cells were grown on permeable filter supports in the absence and presence of DOX (3 or 6 days), and genome-wide transcriptome profiles were assessed using RNA-Seq. We found DOX significantly altered the transcriptome profile, changing the abundance of 1,549 transcripts at 3 days and 2,643 transcripts at 6 days. Within 3 days of treatment, DOX significantly decreased the expression of multiple signaling pathways (ERK, cAMP, and Notch) that are associated with cell proliferation and differentiation. Genes associated with cell cycle progression were subsequently downregulated in cells treated with DOX for 6 days, as were genes involved in cellular immune response processes and several cytokines and chemokines, correlating with a remarkable repression of genes encoding cell proliferation markers. The results provide new insight into responses of renal epithelial cells to DOX and a establish a resource for DOX-mediated gene expression systems.
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影响因子：
3.6
作者：
Das AT;Tenenbaum L;Berkhout B
通讯作者：
Berkhout B
影响因子：
5.3
作者：
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