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Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells

Blood vessels in the brain tissue form a compact vessel structure and play an essential role in maintaining the homeostasis of the neurovascular system. The low dosage of photodynamic intervention (PDT) significantly affects the expression of cellular biomarkers. To understand the impact of photodyn...

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Autores principales: He, Yanyan, Duan, Lin, Wu, Haigang, Chen, Song, Lu, Taoyuan, Li, Tianxiao, He, Yingkun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645902/
https://www.ncbi.nlm.nih.gov/pubmed/34881175
http://dx.doi.org/10.3389/fonc.2021.731414
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author He, Yanyan
Duan, Lin
Wu, Haigang
Chen, Song
Lu, Taoyuan
Li, Tianxiao
He, Yingkun
author_facet He, Yanyan
Duan, Lin
Wu, Haigang
Chen, Song
Lu, Taoyuan
Li, Tianxiao
He, Yingkun
author_sort He, Yanyan
collection PubMed
description Blood vessels in the brain tissue form a compact vessel structure and play an essential role in maintaining the homeostasis of the neurovascular system. The low dosage of photodynamic intervention (PDT) significantly affects the expression of cellular biomarkers. To understand the impact of photodynamic interventions on cerebrovascular endothelial cells, we evaluated the dosage-dependent impact of porfimer sodium-mediated PDT on B.END3 cells using flow cytometer, comet assay, RNA sequencing, and bioinformatics analysis. To examine whether PDT can induce disorder of intracellular organelles, we did not observe any significance damage of DNA and cellular skeleton. Moreover, expression levels of cellular transporters-related genes were significantly altered, implying the drawbacks of PDT on cerebrovascular functions. To address the potential molecular mechanisms of these phenotypes, RNA sequencing and bioinformatics analysis were employed to identify critical genes and pathways among these processes. The gene ontology (GO) analysis and protein-protein interaction (PPI) identified 15 hub genes, highly associated with cellular mitosis process (CDK1, CDC20, MCM5, MCM7, MCM4, CCNA2, AURKB, KIF2C, ESPL1, BUB1B) and DNA replication (POLE2, PLOE, CDC45, CDC6). Gene set enrichment analysis (GSEA) reveals that TNF-α/NF-κB and KRAS pathways may play a critical role in regulating expression levels of transporter-related genes. To further perform qRT-PCR assays, we find that TNF-α/NF-κB and KRAS pathways were substantially up-regulated, consistent with GSEA analysis. The current findings suggested that a low dosage of PDT intervention may be detrimental to the homeostasis of blood-brain barrier (BBB) by inducing the inflammatory response and affecting the expression of surface biomarkers.
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spelling pubmed-86459022021-12-07 Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells He, Yanyan Duan, Lin Wu, Haigang Chen, Song Lu, Taoyuan Li, Tianxiao He, Yingkun Front Oncol Oncology Blood vessels in the brain tissue form a compact vessel structure and play an essential role in maintaining the homeostasis of the neurovascular system. The low dosage of photodynamic intervention (PDT) significantly affects the expression of cellular biomarkers. To understand the impact of photodynamic interventions on cerebrovascular endothelial cells, we evaluated the dosage-dependent impact of porfimer sodium-mediated PDT on B.END3 cells using flow cytometer, comet assay, RNA sequencing, and bioinformatics analysis. To examine whether PDT can induce disorder of intracellular organelles, we did not observe any significance damage of DNA and cellular skeleton. Moreover, expression levels of cellular transporters-related genes were significantly altered, implying the drawbacks of PDT on cerebrovascular functions. To address the potential molecular mechanisms of these phenotypes, RNA sequencing and bioinformatics analysis were employed to identify critical genes and pathways among these processes. The gene ontology (GO) analysis and protein-protein interaction (PPI) identified 15 hub genes, highly associated with cellular mitosis process (CDK1, CDC20, MCM5, MCM7, MCM4, CCNA2, AURKB, KIF2C, ESPL1, BUB1B) and DNA replication (POLE2, PLOE, CDC45, CDC6). Gene set enrichment analysis (GSEA) reveals that TNF-α/NF-κB and KRAS pathways may play a critical role in regulating expression levels of transporter-related genes. To further perform qRT-PCR assays, we find that TNF-α/NF-κB and KRAS pathways were substantially up-regulated, consistent with GSEA analysis. The current findings suggested that a low dosage of PDT intervention may be detrimental to the homeostasis of blood-brain barrier (BBB) by inducing the inflammatory response and affecting the expression of surface biomarkers. Frontiers Media S.A. 2021-11-22 /pmc/articles/PMC8645902/ /pubmed/34881175 http://dx.doi.org/10.3389/fonc.2021.731414 Text en Copyright © 2021 He, Duan, Wu, Chen, Lu, Li and He https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
He, Yanyan
Duan, Lin
Wu, Haigang
Chen, Song
Lu, Taoyuan
Li, Tianxiao
He, Yingkun
Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells
title Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells
title_full Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells
title_fullStr Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells
title_full_unstemmed Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells
title_short Integrated Transcriptome Analysis Reveals the Impact of Photodynamic Therapy on Cerebrovascular Endothelial Cells
title_sort integrated transcriptome analysis reveals the impact of photodynamic therapy on cerebrovascular endothelial cells
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645902/
https://www.ncbi.nlm.nih.gov/pubmed/34881175
http://dx.doi.org/10.3389/fonc.2021.731414
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