Omics · study · 2026
Explore the biological function of mitochondrial metabolism-related genes TSPO in macrophages infiltrating myocarditis
Listed in NCBI GEO
Myocarditis is characterized by infiltration of inflammatory cells in the myocardium.
Description
Treatment is mainly empirical and symptomatic supportive, and there is still a lack of specific treatment strategies for myocarditis. The heart is one of the most energy-demanding organs in the body, and mitochondria are the main places where energy is produced within cells.
To find new therapeutic targets for myocarditis, it is important to explore the biological functions of mitochondria-related genes in myocarditis to find new therapeutic targets for myocarditis. The microarray dataset (GSE35182) was utilized to perform weighted gene co-expression network analysis (WGCNA) to identify the gene module related to myocarditis. The turquoise module was identified to be associated with myocarditis, according to the results of WGCNA.
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We subsequently intersected hub genes in this module with mitochondrial metabolism related genes (MtGs) in MitoCarta3.0 and human myocarditis genes in GeneCards, 2 conserved myocarditis and mitochondrial-related genes were finally identified, namely Glycyl-TRNA Synthetase (Gars) and Translocator Protein (Tspo). In addition, single-cell RNA-sequencing (scRNA-seq) data (GSE174458) was employed to reveal cellular composition in myocarditis.
Macrophages exhibited the highest variation in positive percentage from the control to myocarditis group, and only a significant disparity in Tspo expression was observed within this cluster. Subsequently, we utilized a murine macrophage cell line (RAW264.7 cells) to investigate the biological functions of hub genes. Besides, the down-regulation of Tspo in RAW264.7 cells transfection with siRNA targeting Tspo (si-Tspo) resulted in an augmented inflammatory response, and disruption of mitochondrial function in macrophages upon inflammatory stimulation.
Conversely, the administration of the Tspo ligand Ro5-4864 elicited contrasting effects. Furthermore, according to the enrichment analysis of the RNA-seq data between si-NC+sti and si-Tspo+sti, and fluorescence images indicated by Rhod-2 AM, we supposed that the anti-inflammatory actions of Tspo in macrophages during inflammation were primarily by interfering with the fluxion of Ca2+ into mitochondria. Finally, the administration of Ro5-4864 could mitigate the inflammatory damage induced by CVB3 infection in the heart of mice and protect cardiac function.
Additionally, the potential of hub genes as therapeutic targets was assessed using a viral myocarditis mouse model.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE275nnn/GSE275137 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE275137 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1149672 ncbi.nlm.nih.gov/bioproject/PRJNA1149672 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Mus musculus
- From keywords
- Life Sciences
- Inferred from text
- Heart 75% · Image 65% · RNA sequencing 65% · Single-cell RNA sequencing 65%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE275137 | 7 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[anatomy].local:anatomy:heart | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:image | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[organism].NCBITaxon:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |