Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts

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...
Ausführliche Beschreibung

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Autor*in:	Wenyan Kang [verfasserIn] Zhilong Jia [verfasserIn] Di Tang [verfasserIn] Xiaojing Zhao [verfasserIn] Jinlong Shi [verfasserIn] Qian Jia [verfasserIn] Kunlun He [verfasserIn] Qiang Feng [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	F. nucleatum gingival fibroblasts RNA-seq time-course transcriptome drug repositioning

Übergeordnetes Werk:	In: Frontiers in Cell and Developmental Biology - Frontiers Media S.A., 2014, 7(2019)
Übergeordnetes Werk:	volume:7 ; year:2019

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3389/fcell.2019.00204

Katalog-ID:	DOAJ045357706

Internformat


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520			\|a 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.
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allfields	10.3389/fcell.2019.00204 doi (DE-627)DOAJ045357706 (DE-599)DOAJ7a3cfc724e50427a98c76fd246c5863e DE-627 ger DE-627 rakwb eng QH301-705.5 Wenyan Kang verfasserin aut Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. F. nucleatum gingival fibroblasts RNA-seq time-course transcriptome drug repositioning Biology (General) Wenyan Kang verfasserin aut Zhilong Jia verfasserin aut Zhilong Jia verfasserin aut Di Tang verfasserin aut Xiaojing Zhao verfasserin aut Xiaojing Zhao verfasserin aut Jinlong Shi verfasserin aut Qian Jia verfasserin aut Qian Jia verfasserin aut Kunlun He verfasserin aut Kunlun He verfasserin aut Qiang Feng verfasserin aut Qiang Feng verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 7(2019) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:7 year:2019 https://doi.org/10.3389/fcell.2019.00204 kostenfrei https://doaj.org/article/7a3cfc724e50427a98c76fd246c5863e kostenfrei https://www.frontiersin.org/article/10.3389/fcell.2019.00204/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019
spelling	10.3389/fcell.2019.00204 doi (DE-627)DOAJ045357706 (DE-599)DOAJ7a3cfc724e50427a98c76fd246c5863e DE-627 ger DE-627 rakwb eng QH301-705.5 Wenyan Kang verfasserin aut Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. F. nucleatum gingival fibroblasts RNA-seq time-course transcriptome drug repositioning Biology (General) Wenyan Kang verfasserin aut Zhilong Jia verfasserin aut Zhilong Jia verfasserin aut Di Tang verfasserin aut Xiaojing Zhao verfasserin aut Xiaojing Zhao verfasserin aut Jinlong Shi verfasserin aut Qian Jia verfasserin aut Qian Jia verfasserin aut Kunlun He verfasserin aut Kunlun He verfasserin aut Qiang Feng verfasserin aut Qiang Feng verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 7(2019) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:7 year:2019 https://doi.org/10.3389/fcell.2019.00204 kostenfrei https://doaj.org/article/7a3cfc724e50427a98c76fd246c5863e kostenfrei https://www.frontiersin.org/article/10.3389/fcell.2019.00204/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019
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allfieldsSound	10.3389/fcell.2019.00204 doi (DE-627)DOAJ045357706 (DE-599)DOAJ7a3cfc724e50427a98c76fd246c5863e DE-627 ger DE-627 rakwb eng QH301-705.5 Wenyan Kang verfasserin aut Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. F. nucleatum gingival fibroblasts RNA-seq time-course transcriptome drug repositioning Biology (General) Wenyan Kang verfasserin aut Zhilong Jia verfasserin aut Zhilong Jia verfasserin aut Di Tang verfasserin aut Xiaojing Zhao verfasserin aut Xiaojing Zhao verfasserin aut Jinlong Shi verfasserin aut Qian Jia verfasserin aut Qian Jia verfasserin aut Kunlun He verfasserin aut Kunlun He verfasserin aut Qiang Feng verfasserin aut Qiang Feng verfasserin aut In Frontiers in Cell and Developmental Biology Frontiers Media S.A., 2014 7(2019) (DE-627)770398138 (DE-600)2737824-X 2296634X nnns volume:7 year:2019 https://doi.org/10.3389/fcell.2019.00204 kostenfrei https://doaj.org/article/7a3cfc724e50427a98c76fd246c5863e kostenfrei https://www.frontiersin.org/article/10.3389/fcell.2019.00204/full kostenfrei https://doaj.org/toc/2296-634X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 7 2019
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callnumber-first	Q - Science
author	Wenyan Kang
spellingShingle	Wenyan Kang misc QH301-705.5 misc F. nucleatum misc gingival fibroblasts misc RNA-seq misc time-course transcriptome misc drug repositioning misc Biology (General) Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts
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topic_title	QH301-705.5 Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts F. nucleatum gingival fibroblasts RNA-seq time-course transcriptome drug repositioning
topic	misc QH301-705.5 misc F. nucleatum misc gingival fibroblasts misc RNA-seq misc time-course transcriptome misc drug repositioning misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc F. nucleatum misc gingival fibroblasts misc RNA-seq misc time-course transcriptome misc drug repositioning misc Biology (General)
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title	Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts
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title_full	Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts
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title_sort	time-course transcriptome analysis for drug repositioning in fusobacterium nucleatum-infected human gingival fibroblasts
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title_auth	Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts
url	https://doi.org/10.3389/fcell.2019.00204 https://doaj.org/article/7a3cfc724e50427a98c76fd246c5863e https://www.frontiersin.org/article/10.3389/fcell.2019.00204/full https://doaj.org/toc/2296-634X
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author2	Wenyan Kang Zhilong Jia Di Tang Xiaojing Zhao Jinlong Shi Qian Jia Kunlun He Qiang Feng
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up_date	2024-07-03T14:30:39.126Z
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Time-Course Transcriptome Analysis for Drug Repositioning in Fusobacterium nucleatum-Infected Human Gingival Fibroblasts

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