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pmid:35186462
Cathepsin S are involved in human carotid atherosclerotic disease progression, mainly by mediating phagosomes: bioinformatics and in vivo and vitro experiments.
Hailong Wang · Haiying Jiang · Xian Wu Cheng
PeerJ · 2022 doi:10.7717/peerj.12846
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Complete file
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Animal experiments have indicated that cathepsins (CTSs) mediate the antigen transmission and inflammatory response involved in the atherosclerosis process, but the specific signal pathways and target cells of the CTSs involved in atherosclerosis are unknown.\nMETHODS: We used the GEO query package to download the dataset GSE28829 from the Gene Expression Omnibus (GEO) and filtered the data to check the standardization of the samples through the box chart. We then used the 'limma' package to analyze between-group differences and selected the corresponding differentially expressed genes of CTSs from the protein-protein interaction (PPI) network constructed with the STRING database, and then visualized the CTS-target genes. The best matching pathway and target cells were verified by a male mouse ligation experiment, single-sample GSEA (ssGSEA) analysis, and vitro experiment.\nRESULTS: There were 275 differentially expressed genes (DEGs) selected from the GSE28829 dataset, and the DEGs were identified mainly in the PPI network; 58 core genes (APOE, CD74, CP, AIF1, etc.) target three selected CTS family members (CTSS, CTSB, and CTSC). After the enriched analysis, 15 CTS-target genes were markedly enriched in the phagosome signaling pathway. The mouse experiment results revealed that the percentages and numbers of monocytes and neutrophils and the number of CD68+ cells in CTSS deficiency (CatS-/-) group were lower than those in the wildtype (CatS+/+) group. CTSS mediating phagosome via macrophage were further verified by ssGSEA analysis and vitro experiment.\nCONCLUSIONS: CTSS are the main target molecules in the CTS family that are involved in atherosclerosis. The molecule participate in the progression of atherosclerosis by mediating the phagosome via macrophage.", "claims": [{"id": "claim-method", "statement": "Finally, we used the \"limma\" R package to conduct CSE28829 differentially expressed gene (DEG) screening at | log2 (fold-change)| >1, and we set adjusted p-values <0.05 as the thresholds of the DEG screening.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35186462", "locator": "sections[4] \"Data preprocessing and DEG screening\" paragraph 2", "quote": "Finally, we used the \"limma\" R package to conduct CSE28829 differentially expressed gene (DEG) screening at | log2 (fold-change)| >1, and we set adjusted p-values <0.05 as the thresholds of the DEG screening."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data is available in the Supplemental Files and at GEO: GSE28829.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35186462", "locator": "sections[35] \"Data Availability\" paragraph 2", "quote": "The raw data is available in the Supplemental Files and at GEO: GSE28829."}], "state": "complete"}, {"id": "claim-target-result", "statement": "There were 275 differentially expressed genes (DEGs) selected from the GSE28829 dataset.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35186462", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "There were 275 differentially expressed genes (DEGs) selected from the GSE28829 dataset, and the DEGs were identified mainly in the PPI network; 58 core genes (APOE, CD74, CP, AIF1, etc.) target three selected CTS family members (CTSS, CTSB, and CTSC)."}, {"asset": "source:pmid:35186462", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We used the GEO query package to download the dataset GSE28829 from the Gene Expression Omnibus (GEO) and filtered the data to check the standardization of the samples through the box chart."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "There were 275 differentially expressed genes (DEGs) selected from the GSE28829 dataset.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:35186462"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE28829"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE28829"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35186462", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.12846", "sha256": "sha256:13403fd7c71b18827776b26155872436546f625c3c5e05adfdbfb13fa63c6bd6", "bytes": 40339, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.12846", "version": null, "note": "Full article fetched from PMC; 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