Identification of key genes in sepsis-induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivo

Introduction Sepsis is a life-threatening disease that damages multiple organs and induced by the host’s dysregulated response to infection with high morbidity and mortality. Heart remains one of the most vulnerable targets of sepsis-induced organ damage, and sepsis-induced cardiomyopathy (SIC) is a...

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Main Authors: Dehua Liu, Tao Wang, Qingguo Wang, Peikang Dong, Xiaohong Liu, Qiang Li, Youkui Shi, Jingtian Li, Jin Zhou, Quan Zhang
Format: Article
Language:English
Published: PeerJ Inc. 2023-11-01
Series:PeerJ
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Online Access:https://peerj.com/articles/16222.pdf
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author Dehua Liu
Tao Wang
Qingguo Wang
Peikang Dong
Xiaohong Liu
Qiang Li
Youkui Shi
Jingtian Li
Jin Zhou
Quan Zhang
author_facet Dehua Liu
Tao Wang
Qingguo Wang
Peikang Dong
Xiaohong Liu
Qiang Li
Youkui Shi
Jingtian Li
Jin Zhou
Quan Zhang
author_sort Dehua Liu
collection DOAJ
description Introduction Sepsis is a life-threatening disease that damages multiple organs and induced by the host’s dysregulated response to infection with high morbidity and mortality. Heart remains one of the most vulnerable targets of sepsis-induced organ damage, and sepsis-induced cardiomyopathy (SIC) is an important factor that exacerbates the death of patients. However, the underlying genetic mechanism of SIC disease needs further research. Methods The transcriptomic dataset, GSE171564, was downloaded from NCBI for further analysis. Gene expression matrices for the sample group were obtained by quartile standardization and log2 logarithm conversion prior to analysis. The time series, protein-protein interaction (PPI) network, and functional enrichment analysis via Gene Ontology and KEGG Pathway Databases were used to identify key gene clusters and their potential interactions. Predicted miRNA-mRNA relationships from multiple databases facilitated the construction of a TF-miRNA-mRNA regulatory network. In vivo experiments, along with qPCR and western blot assays, provided experimental validation. Results The transcriptome data analysis between SIC and healthy samples revealed 221 down-regulated, and 342 up-regulated expressed genes across two distinct clusters. Among these, Tpt1, Mmp9 and Fth1 were of particular significance. Functional analysis revealed their role in several biological processes and pathways, subsequently, in vivo experiments confirmed their overexpression in SIC samples. Notably, we found TPT1 play a pivotal role in the progression of SIC, and silencing TPT1 showed a protective effect against LPS-induced SIC. Conclusion In our study, we demonstrated that Tpt1, Mmp9 and Fth1 have great potential to be biomarker of SIC. These findings will facilitated to understand the occurrence and development mechanism of SIC.
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spelling doaj.art-199d37f9854f40eb971baa568f55991e2023-11-23T15:05:07ZengPeerJ Inc.PeerJ2167-83592023-11-0111e1622210.7717/peerj.16222Identification of key genes in sepsis-induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivoDehua Liu0Tao Wang1Qingguo Wang2Peikang Dong3Xiaohong Liu4Qiang Li5Youkui Shi6Jingtian Li7Jin Zhou8Quan Zhang9Weifang Medical University, Weifang, ChinaDepartment of Cardiology, Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Cardiology, Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Cardiology, Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Cardiology, Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Cardiology, Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Emergency Medicine, Affiliated Hospital of Weifang Medical University, Weifang, ChinaDepartment of Cardiology, Affiliated Hospital of Weifang Medical University, Weifang, ChinaSchool of Pharmacy, Weifang Medical University, Weifang, ChinaDepartment of Cardiology, Affiliated Hospital of Weifang Medical University, Weifang, ChinaIntroduction Sepsis is a life-threatening disease that damages multiple organs and induced by the host’s dysregulated response to infection with high morbidity and mortality. Heart remains one of the most vulnerable targets of sepsis-induced organ damage, and sepsis-induced cardiomyopathy (SIC) is an important factor that exacerbates the death of patients. However, the underlying genetic mechanism of SIC disease needs further research. Methods The transcriptomic dataset, GSE171564, was downloaded from NCBI for further analysis. Gene expression matrices for the sample group were obtained by quartile standardization and log2 logarithm conversion prior to analysis. The time series, protein-protein interaction (PPI) network, and functional enrichment analysis via Gene Ontology and KEGG Pathway Databases were used to identify key gene clusters and their potential interactions. Predicted miRNA-mRNA relationships from multiple databases facilitated the construction of a TF-miRNA-mRNA regulatory network. In vivo experiments, along with qPCR and western blot assays, provided experimental validation. Results The transcriptome data analysis between SIC and healthy samples revealed 221 down-regulated, and 342 up-regulated expressed genes across two distinct clusters. Among these, Tpt1, Mmp9 and Fth1 were of particular significance. Functional analysis revealed their role in several biological processes and pathways, subsequently, in vivo experiments confirmed their overexpression in SIC samples. Notably, we found TPT1 play a pivotal role in the progression of SIC, and silencing TPT1 showed a protective effect against LPS-induced SIC. Conclusion In our study, we demonstrated that Tpt1, Mmp9 and Fth1 have great potential to be biomarker of SIC. These findings will facilitated to understand the occurrence and development mechanism of SIC.https://peerj.com/articles/16222.pdfSepsis-induced cardiomyopathyTPT1PPIHub gene
spellingShingle Dehua Liu
Tao Wang
Qingguo Wang
Peikang Dong
Xiaohong Liu
Qiang Li
Youkui Shi
Jingtian Li
Jin Zhou
Quan Zhang
Identification of key genes in sepsis-induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivo
PeerJ
Sepsis-induced cardiomyopathy
TPT1
PPI
Hub gene
title Identification of key genes in sepsis-induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivo
title_full Identification of key genes in sepsis-induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivo
title_fullStr Identification of key genes in sepsis-induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivo
title_full_unstemmed Identification of key genes in sepsis-induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivo
title_short Identification of key genes in sepsis-induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivo
title_sort identification of key genes in sepsis induced cardiomyopathy based on integrated bioinformatical analysis and experiments in vitro and in vivo
topic Sepsis-induced cardiomyopathy
TPT1
PPI
Hub gene
url https://peerj.com/articles/16222.pdf
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