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pmid:36899394
Identification of Timm13 protein translocase of the mitochondrial inner membrane as a potential mediator of liver fibrosis based on bioinformatics and experimental verification.
Xiaomin Liao · Xianxian Ruan · Xianbin Wu · Zhejun Deng · Shanyu Qin · Haixing Jiang
Journal of translational medicine · 2023 doi:10.1186/s12967-023-04037-2
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Complete file
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Differentially expressed genes (DEGs) between liver disease and normal samples were analyzed using GEO2R. Gene Ontology and Enrichment function were performed, a protein-protein interaction (PPI) network was constructed via the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and the hub genes of the PPI network were calculated by MCODE plug-in in Cytoscape. We validated the transcriptional and post-transcriptional expression levels of the top correlated genes using fibrotic animal and cell models. A cell transfection experiment was conducted to silence Timm13 and detect the expression of fibrosis genes and apoptosis genes.\nRESULTS: 21,722 genes were analyzed and 178 DEGs were identified by GEO2R analysis. The top 200 DEGs were selected and analyzed in STRING for PPI network analysis. Timm13 was one of the hub genes via the PPI network. We found that the mRNA levels of Timm13 in fibrotic liver tissue decreased (P < 0.05), and the mRNA and protein levels of Timm13 also decreased when hepatocytes were stimulated with transforming growth factor-β1. Silencing Timm13 significantly reduced the expression of profibrogenic genes and apoptosis related genes.\nCONCLUSIONS: The results showed that Timm13 is closely related to liver fibrosis and silencing Timm13 significantly reduced the expression of profibrogenic genes and apoptosis related genes, which will provide novel ideas and targets for the clinical diagnosis and treatment of liver fibrosis.", "claims": [{"id": "claim-method", "statement": "Data were compared with the Student’s t-test and one-way analysis of variance (ANOVA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36899394", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "Data were compared with the Student’s t-test and one-way analysis of variance (ANOVA)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used to support the findings of this study are included within the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36899394", "locator": "sections[33] \"notes\" paragraph 1", "quote": "The data used to support the findings of this study are included within the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The results showed that Timm13 is closely related to liver fibrosis and silencing Timm13 significantly reduced the expression of profibrogenic genes and apoptosis related genes, which will provide novel ideas and targets for the clinical diagnosis and treatment of liver fibrosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36899394", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The results showed that Timm13 is closely related to liver fibrosis and silencing Timm13 significantly reduced the expression of profibrogenic genes and apoptosis related genes, which will provide novel ideas and targets for the clinical diagnosis and treatment of liver fibrosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The results showed that Timm13 is closely related to liver fibrosis and silencing Timm13 significantly reduced the expression of profibrogenic genes and apoptosis related genes, which will provide novel ideas and targets for the clinical diagnosis and treatment of liver fibrosis.", "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:36899394"], "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. 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A cell transfection experiment was conducted to silence Timm13 a"], "order_basis": "paper_text_order:889", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["detect the expression of fibrosis genes and apoptosis genes. RESULTS: 21,722 genes were analyzed a", "ed the expression of profibrogenic genes and apoptosis related genes. CONCLUSIONS: The results show", "ed the expression of profibrogenic genes and apoptosis related genes, which will provide novel idea"], "order_basis": "paper_text_order:994", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["cant enrichment function. 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