细胞生物学
信号转导
转录因子
激活转录因子
基因剔除小鼠
癌症研究
生物
化学
未折叠蛋白反应
内质网
受体
基因
生物化学
作者
Fengmei Song,Shuang Li,Xuyan Dai,Fei Yang,Yi Cao
出处
期刊:Molecular omics
[The Royal Society of Chemistry]
日期:2023-01-01
卷期号:19 (2): 150-161
被引量:3
摘要
Although titanium (Ti)-based nanomaterials (NMs) were traditionally considered as biologically inert materials, it was recently reported that Ti-based NMs induce adverse vascular effects by inhibiting Kruppel-like factor 2 (KLF2) and/or KLF4, vasoprotective KLFs with well-documented regulatory activity in NO signaling. However, the potential roles of other KLFs are not clear. KLF6 was recently identified as an important KLF involved in regulating endothelial dysfunction, inflammation, and angiogenesis, therefore, this study investigated the influence of titanate nanofibers (TiNFs) on KLF6-mediated events. Ingenuity pathway analysis (IPA) showed that TiNFs altered the expression of a panel of KLF6-related genes: KLF6-mediated gene ontology (GO) terms were altered, categories including cytokine-mediated signaling pathways, transcription factor (TF) functions and membrane-bound organelles. Additionally, RT-PCR confirmed that TiNFs increased KLF6 activating transcription factor 3 (ATF3), a TF involved in endoplasmic reticulum (ER) stress, and ELISA confirmed the increase of soluble monocyte chemotactic protein 1 (sMCP-1), a KLF6-related inflammatory cytokine. Interestingly, the activation of klf6, atf3 and C-C motif chemokine ligand 2 (ccl2; mcp-1 encoding gene) was observed in aortas of mice following one-time intravenous injection but not intratracheal instillation of TiNFs (100 μg per mouse), indicating a need for direct contact with NMs to activate klf6-mediated pathways in vivo. In endothelial cells, KLF6 knockdown inhibited the expression of ATF3 but not CCL2, suggesting the regulatory role of KLF6 in ATF3 expression. Overall, this study uncovered a previously unknown role of KLF6 in TiNF-induced vascular effects both in vitro and in vivo.
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