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Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation
Septic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autop...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378994/ https://www.ncbi.nlm.nih.gov/pubmed/35983185 http://dx.doi.org/10.3389/fcvm.2022.923066 |
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author | Zou, Hua-Xi Qiu, Bai-Quan Zhang, Ze-Yu Hu, Tie Wan, Li Liu, Ji-Chun Huang, Huang Lai, Song-Qing |
author_facet | Zou, Hua-Xi Qiu, Bai-Quan Zhang, Ze-Yu Hu, Tie Wan, Li Liu, Ji-Chun Huang, Huang Lai, Song-Qing |
author_sort | Zou, Hua-Xi |
collection | PubMed |
description | Septic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autophagy in the pathogenesis of SCM remains limited and uncertain. Exploring the molecular mechanisms of disease based on the transcriptomes of human pathological samples may bring the closest insights. In this study, we analyzed the differential expression of autophagy-related genes in SCM based on the transcriptomes of human septic hearts, and further explored their potential crosstalk and functional pathways. Key functional module and hub genes were identified by constructing a protein–protein interaction network. Eight key genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) that regulate autophagy in SCM were identified after validation in a lipopolysaccharide (LPS)-induced H9c2 cardiomyoblast injury model, as well as the autophagic characteristic features. Furthermore, we found that key genes were associated with abnormal immune infiltration in septic hearts and have the potential to serve as biomarkers. Finally, we predicted drugs that may play a protective role in SCM by regulating autophagy based on our results. Our study provides evidence and new insights into the role of autophagy in SCM based on human septic heart transcriptomes, which would be of great benefit to reveal the molecular pathological mechanisms and explore the diagnostic and therapeutic targets for SCM. |
format | Online Article Text |
id | pubmed-9378994 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93789942022-08-17 Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation Zou, Hua-Xi Qiu, Bai-Quan Zhang, Ze-Yu Hu, Tie Wan, Li Liu, Ji-Chun Huang, Huang Lai, Song-Qing Front Cardiovasc Med Cardiovascular Medicine Septic cardiomyopathy (SCM) is severe organ dysfunction caused by sepsis that is associated with poor prognosis, and its pathobiological mechanisms remain unclear. Autophagy is a biological process that has recently been focused on SCM, yet the current understanding of the role of dysregulated autophagy in the pathogenesis of SCM remains limited and uncertain. Exploring the molecular mechanisms of disease based on the transcriptomes of human pathological samples may bring the closest insights. In this study, we analyzed the differential expression of autophagy-related genes in SCM based on the transcriptomes of human septic hearts, and further explored their potential crosstalk and functional pathways. Key functional module and hub genes were identified by constructing a protein–protein interaction network. Eight key genes (CCL2, MYC, TP53, SOD2, HIF1A, CTNNB1, CAT, and ADIPOQ) that regulate autophagy in SCM were identified after validation in a lipopolysaccharide (LPS)-induced H9c2 cardiomyoblast injury model, as well as the autophagic characteristic features. Furthermore, we found that key genes were associated with abnormal immune infiltration in septic hearts and have the potential to serve as biomarkers. Finally, we predicted drugs that may play a protective role in SCM by regulating autophagy based on our results. Our study provides evidence and new insights into the role of autophagy in SCM based on human septic heart transcriptomes, which would be of great benefit to reveal the molecular pathological mechanisms and explore the diagnostic and therapeutic targets for SCM. Frontiers Media S.A. 2022-08-02 /pmc/articles/PMC9378994/ /pubmed/35983185 http://dx.doi.org/10.3389/fcvm.2022.923066 Text en Copyright © 2022 Zou, Qiu, Zhang, Hu, Wan, Liu, Huang and Lai. 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 | Cardiovascular Medicine Zou, Hua-Xi Qiu, Bai-Quan Zhang, Ze-Yu Hu, Tie Wan, Li Liu, Ji-Chun Huang, Huang Lai, Song-Qing Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
title | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
title_full | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
title_fullStr | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
title_full_unstemmed | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
title_short | Dysregulated autophagy-related genes in septic cardiomyopathy: Comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
title_sort | dysregulated autophagy-related genes in septic cardiomyopathy: comprehensive bioinformatics analysis based on the human transcriptomes and experimental validation |
topic | Cardiovascular Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378994/ https://www.ncbi.nlm.nih.gov/pubmed/35983185 http://dx.doi.org/10.3389/fcvm.2022.923066 |
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