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, Jichun; Huang, Huang; Lai, Songqing

doi:10.3389/fcvm.2022.923066

Cited by 3 publications

(7 citation statements)

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“…As described in our previous study, 29 the microarray datasets GSE79962 and GSE54514 were retrieved from the GEO database (https://www.ncbi.nlm.nih.gov/geo/). The transcriptomic data of 11 control hearts (sourced from non-failed donors) and 20 septic hearts (sourced from patients who died from sepsis) were obtained from the GSE79962 dataset, while the transcriptomic data of whole blood samples (within 24 hours of admission to the intensive care unit) from 26 sepsis survivors and 9 sepsis nonsurvivors were obtained from the GSE54514 dataset.…”

Section: Data Collectionmentioning

confidence: 99%

“…As described in our previous study, 29 the identified DEFRGs were subjected to GO and KEGG enrichment analyses using the clusterProfiler package in the R software. 34 FDR < 0.05 was the criterion for significantly enriched by DEFRGs.…”

Section: Gene Ontology (Go) and Kyoto Encyclopedia Of Genes And Genom...mentioning

confidence: 99%

“…The STRING database (https://string-db.org/) and Cytoscape software were used to establish and visualize a PPI network of DEFRGs as described in our previous studies. 29 Functional key modules were identified from the PPI network by the MCODE plugin using the K-means clustering algorithm (degree cutoff = 2, node score cutoff = 0.2, K-core = 2). The genes in the PPI network were assigned and ranked accordingly by Cytohubba's built-in MCC algorithm, and the top ten genes were screened as hub genes.…”

Section: Ppi Network and Identification Of Key Modules And Hub Genesmentioning

confidence: 99%

“…Western blotting was performed as described in our previous study. 29 Briefly, the myocardium (with removal of atriums) was homogenized and lysed, and the extracted proteins were separated by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to PVDF membranes. After blocking with 5% non-fat dry milk at room temperature for 2 hours, the blots were incubated overnight with primary antibodies against PTGS2 (Proteintech #12375-1-AP, China, 1:1000) and β-actin (Biosharp #BL005B, China, 1:2000) at 4°C.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…The protocol for qRT-PCR has been described in our previous study. 29 Briefly, myocardia (with removal of atriums) were homogenized in TRIzol (Invitrogen, USA) to extract total RNA. After removal of genomic DNA by DNase treatment, total RNA was then reverse-transcribed into cDNA using RevertAid MM (ThermoFisher Scientific, USA) according to the manufacturer's instruction.…”

Section: Western Blot Analysismentioning

confidence: 99%

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Exploring Dysregulated Ferroptosis-Related Genes in Septic Myocardial Injury Based on Human Heart Transcriptomes: Evidence and New Insights

Zou¹,

Hu²,

Zhao³

et al. 2023

JIR

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Introduction: Sepsis is currently a common condition in emergency and intensive care units, and is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Cardiac dysfunction caused by septic myocardial injury (SMI) is associated with adverse prognosis and has significant economic and human costs. The pathophysiological mechanisms underlying SMI have long been a subject of interest. Recent studies have identified ferroptosis, a form of programmed cell death associated with iron accumulation and lipid peroxidation, as a pathological factor in the development of SMI. However, the current understanding of how ferroptosis functions and regulates in SMI remains limited, particularly in the absence of direct evidence from human heart. Methods: We performed a sequential comprehensive bioinformatics analysis of human sepsis cardiac transcriptome data obtained through the GEO database. The lipopolysaccharide-induced mouse SMI model was used to validate the ferroptosis features and transcriptional expression of key genes. Results: We identified widespread dysregulation of ferroptosis-related genes (FRGs) in SMI based on the human septic heart transcriptomes, deeply explored the underlying biological mechanisms and crosstalks, followed by the identification of key functional modules and hub genes through the construction of protein-protein interaction network. Eight key FRGs that regulate ferroptosis in SMI, including HIF1A, MAPK3, NOX4, PPARA, PTEN, RELA, STAT3 and TP53, were identified, as well as the ferroptosis features. All the key FRGs showed excellent diagnostic capability for SMI, part of them was associated with the prognosis of sepsis patients and the immune infiltration in the septic hearts, and potential ferroptosis-modulating drugs for SMI were predicted based on key FRGs. Conclusion:This study provides human septic heart transcriptome-based evidence and brings new insights into the role of ferroptosis in SMI, which is significant for expanding the understanding of the pathobiological mechanisms of SMI and exploring promising diagnostic and therapeutic targets for SMI.

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Section: Data Collectionmentioning

confidence: 99%

Section: Gene Ontology (Go) and Kyoto Encyclopedia Of Genes And Genom...mentioning

confidence: 99%

Section: Ppi Network and Identification Of Key Modules And Hub Genesmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

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