KLF4公司
转录因子
ATF3
激活转录因子
细胞生物学
化学
体外
基因表达
体内
生物
分子生物学
基因
生物化学
遗传学
发起人
SOX2
作者
Wandi Cao,Mingkang Liu,Canyang Wang,Guoxing Jing,Yi Cao
摘要
Abstract Kruppel‐like factors (KLFs) are a set of transcription factors (TFs) involved in the regulation of many basic biological processes, and recent studies suggested that nanoparticles (NPs) were capable to change KLFs in different models even at non‐cytotoxic concentrations. In this study, we repeatedly exposed 3D Caco‐2 spheroids and mice to TiO 2 NPs, one of the most frequently used metal oxide NPs, and investigated the changes of KLF‐signaling pathways based on RNA‐sequencing. Although the internalization of TiO 2 NPs did not induce cytotoxicity in vitro, repeated exposure (three times within 7 days) to 15.7 ng/ml TiO 2 NPs increased KLF4 but decreased KLF6. Consistently, KLF4/KLF6‐regulated gene ontology terms were altered, including those involved in the regulation of gene expression. We further verified that repeated exposure to 15.7 ng/ml TiO 2 NPs increased the expression of KLF4 and proto‐oncogene, bHLH transcription factor (MYC), but decreased the expression of KLF6 and activating transcription factor 3 (ATF3). But with the increase of NP concentrations, the expression of these genes was decreased. In mice following intragastrical exposure to 4.39 and 43.9 mg/kg TiO 2 NPs (once a day for 5 continuous days), we observed increased expression of klf4, klf6, myc, and atf3, along with morphological changes of intestines. We concluded that repeated exposure to low levels of TiO 2 NPs altered KLF‐signaling pathways in intestinal cells both in vitro and in vivo.
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