10.3389/fcell.2019.00204.s002
Wenyan Kang
Wenyan
Kang
Zhilong Jia
Zhilong
Jia
Di Tang
Di
Tang
Xiaojing Zhao
Xiaojing
Zhao
Jinlong Shi
Jinlong
Shi
Qian Jia
Qian
Jia
Kunlun He
Kunlun
He
Qiang Feng
Qiang
Feng
Image_2_Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts.TIF
Frontiers
2019
F. nucleatum
gingival fibroblasts
RNA-seq
time-course transcriptome
drug repositioning
2019-09-24 15:14:27
Figure
https://frontiersin.figshare.com/articles/figure/Image_2_Time-Course_Transcriptome_Analysis_for_Drug_Repositioning_in_Fusobacterium_nucleatum-Infected_Human_Gingival_Fibroblasts_TIF/9897644
<p>Fusobacterium nucleatum (F. nucleatum) is a crucial periodontal pathogen and human gingival fibroblasts (GFs) are the first line of defense against oral pathogens. However, the research on potential molecular mechanisms of host defense and effective treatment of F. nucleatum infection in GFs remains scarce. In this study, we undertook a time-series experiment and performed an RNA-seq analysis to explore gene expression profiles during the process of F. nucleatum infection in GFs. Differentially expressed genes (DEGs) could be divided into three coexpression clusters. Functional analysis revealed that the immune-related signaling pathways were more overrepresented at the early stage, while metabolic pathways were mainly enriched at the late stage. We computationally identified several U.S. Food and Drug Administration (FDA)-approved drugs that could protect the F. nucleatum infected GFs via a coexpression-based drug repositioning approach. Biologically, we confirmed that six drugs (etravirine, zalcitabine, wortmannin, calcium D-pantothenate, ellipticine, and tanespimycin) could significantly decrease F. nucleatum-induced reactive oxygen species (ROS) generation and block the Protein Kinase B (PKB/AKT)/mitogen-activated protein kinase signaling pathways. Our study provides more detailed molecular mechanisms of the process by which F. nucleatum infects GFs and illustrates the value of the cogena-based drug repositioning method and the potential therapeutic application of these tested drugs in the treatment of F. nucleatum infection.</p>