The mTOR-RUNX1 pathway regulates DC-SIGN expression in renal tubular epithelial cells.
The mTOR-RUNX1 pathway regulates DC-SIGN expression in renal tubular epithelial cells.
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mTOR-RUNX1 通路调节肾小管上皮细胞中 DC-SIGN 的表达。
DOI：
10.1016/j.bbrc.2019.09.042
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发表时间：
2019-11
期刊：
影响因子：
--
通讯作者：
Zhou Tong
中科院分区：
文献类型：
--
作者：
Zhou Siyuan;Zhang Liya;Feng Danying;Luo Maocai;Xie Rongli;Yang Kaige;Xu Dan;Yang Ke;Fei Jian;Zhou Tong
肾小管上皮细胞（RTEC）在肾脏的先天性免疫反应中起着关键作用。树突状细胞特异性细胞内粘附分子3抓取非整合素（DC-SIGN）既是天然免疫识别受体又是粘附分子。在我们之前的研究中，我们发现在肾脏炎症过程中，DC-SIGN表达在RTECs中被诱导。然而，其潜在机制仍不清楚。本研究以人近端肾小管上皮细胞系（HK-2）为研究对象，探讨TNF-α诱导DC-SIGN表达的机制。结果表明，TNF-α以时间依赖性方式上调DC-SIGN和Runt-related transcription factor 1（RUNX1）的表达，并以剂量依赖性方式上调DC-SIGN启动子驱动的荧光素酶活性。mTOR抑制剂雷帕霉素和mTOR siRNA阻断TNF-α诱导的DC-SIGN表达上调。同时，RUNX 1 siRNA及其抑制剂Ro 5 - 3335也抑制了DC-SIGN的表达。此外，mTOR和RUNX1抑制剂均减弱了TNF-α诱导的DC-SIGN启动子驱动的荧光素酶活性增加。最后，我们发现暴露于雷帕霉素或mTOR siRNA的HK-2细胞减少了TNF-α诱导的RUNX1上调。总之，这些结果表明，mTOR-RUNX1通路参与调节TNF-α诱导的RTECs中DC-SIGN表达。
Renal tubular epithelial cells (RTECs) play pivotal roles in the innate immune response in kidneys. Dendritic cell specific intracellular adhesion molecule–3 grabbing nonintegrin (DC-SIGN) functions as both the innate immune recognition receptor and the adhesion molecule. In our previous study, we found that DC-SIGN expression was induced in RTECs during renal inflammation. However, the underlying mechanism remains unclear. Here, we used the human renal proximal tubular epithelial cell lines (HK-2) to investigate the mechanism of TNF-α-induced expression of DC-SIGN. Our results showed that TNF-α up-regulated the expressions of DC-SIGN and Runt-related transcription factor 1 (RUNX1) in a time-dependent manner and that it up-regulated DC-SIGN promoter-driven luciferase activity in a dose-dependent manner. The mTOR inhibitor rapamycin and mTOR siRNA blocked the TNF-α-induced up-regulation of DC-SIGN expression. Meanwhile, DC-SIGN expression was also inhibited by RUNX1 siRNA and its inhibitor Ro5-3335. In addition, both mTOR and RUNX1 inhibitors attenuated TNF-α-induced the increase in DC-SIGN promoter-driven luciferase activity. Finally, we found that HK-2 cells exposed to rapamycin or mTOR siRNA reduced the TNF-α-induced up-regulation of RUNX1. In conclusion, these results indicated that the mTOR-RUNX1 pathway participates in the regulation of TNF-α-induced DC-SIGN expression in RTECs.
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影响因子：
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作者：
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DOI：
--
发表时间：
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