Citation: Shuang Li, Xuejun Zheng, Chaobo Huang, Yi Cao. Titanate nanofibers reduce Kruppel-like factor 2 (KLF2)-eNOS pathway in endothelial monolayer: A transcriptomic study[J]. Chinese Chemical Letters, ;2021, 32(4): 1567-1570. doi: 10.1016/j.cclet.2020.10.044 shu

Titanate nanofibers reduce Kruppel-like factor 2 (KLF2)-eNOS pathway in endothelial monolayer: A transcriptomic study

Shuang Li ^a ,
Xuejun Zheng ^a ,
Chaobo Huang ^b ,
Yi Cao ^{a, *,}

a.
School of Mechanical Engineering, Xiangtan University, Xiangtan 411105, China
b.
College of Chemical Engineering, Nanjing Forestry University (NFU), Nanjing 210037, China

caoyi39@126.com

Received Date: 11 October 2020
Revised Date: 29 October 2020
Accepted Date: 29 October 2020
Available Online: 29 October 2020

Figures(4)

Although titanate nanofibers (TiNFs) and titanate nanotubes (TiNTs) have been proposed as relatively biocompatible nanomaterials (NMs), there is currently lacking of systemic studies which investigated the toxicity of TiNFs and TiNTs to endothelium. In this study, we developed endothelial monolayer model by using cell culture inserts, and systemically investigated the toxicity of TiNFs and TiNTs by RNA-seq, with a focus on Kruppel-like factor (KLF)-mediated effects, since KLF are transcription factors (TF) involved in the regulation of vascular biology. It was shown that NMs did not significantly induce cytotoxicity despite substantial internalization. However, the expression of many KLF was altered, and Western blot further confirmed that NMs down-regulated KLF2 proteins. Ingenuity pathway analysis (IPA) revealed that NMs altered the expression of KLF2-targed genes, typically the genes involved in inflammatory responses. KLF2-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways were also altered, and it should be noticed that NMs altered GO terms and KEGG pathways related with endothelial NO synthase (eNOS). This study further verified that NMs decreased intracellular NO and eNOS proteins. All the observed effects were more obvious for TiNFs compared with TiNTs. Combined, this study showed that TiNFs or TiNTs were non-cytotoxic to endothelial monolayer model, but TiNFs and more modestly TiNTs decreased KLF2 leading to decreased eNOS proteins and NO production. Our data may provide novel understanding about the toxicity of TiNFs as well as other Ti-based NMs to endothelium.
- Titanate,
- Nanofibers,
- Kruppel-like factor 2 (KLF2),
- Endothelial monolayer,
- Endothelial NO synthase (eNOS),
- Transcriptomics
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