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pmid:39172111
Acyl-CoA thioesterase 13 (ACOT13) attenuates the progression of autosomal dominant polycystic kidney disease in vitro via triggering mitochondrial-related cell apoptosis.
Bin Wang · Qi Yang · Lihe Che · Luyao Sun · Na Du
Aging · 2024 doi:10.18632/aging.206054
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Experiment
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Data
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Analysis
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Execution
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Complete file
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It has been shown that Acyl-CoA thioesterase 13 (ACOT13) level was reduced in renal cystic tissues from ADPKD patients. However, the role of ACOT13 in ADPKD remains largely elusive.\nMETHODS: The data in the GSE7869 dataset were acquired from the GEO database to determine ACOT13 level between normal renal cortical tissues and renal cystic tissues. Next, the potential functions of ACOT13 were explored by gene set enrichment analysis (GSEA). Furthermore, ACOT13 level in ADPKD cells (WT9-12) was verified by RT-qPCR. The effects of ACOT13 on WT9-12 cell growth were evaluated using the EdU staining and flow cytometry assays.\nRESULTS: Compared to normal group, ACOT13 mRNA level was obviously reduced in renal cystic tissues and WT9-12 cells. Meanwhile, GSEA results showed that compared to the low ACOT13 expression group, PI3K-Akt and MAPK signaling pathways were inactivated, and PPAR signaling pathway and fatty acid metabolism were activated in high ACOT13 expression group. Furthermore, overexpression of ACOT13 notably reduced WT9-12 cell proliferation and triggered cell cycle arrest. Moreover, ACOT13 overexpression remarkably triggered apoptosis, increased cleaved caspase 3 protein level, reduced ATP production and induced loss of mitochondrial membrane potential in WT9-12 cells, suggesting that ACOT13 overexpression could trigger mitochondrial-related apoptosis in WT9-12 cells.\nCONCLUSIONS: Collectively, our results showed that overexpression of ACOT13 could suppress WT9-12 cell proliferation and trigger mitochondrial-mediated cell apoptosis, suggesting that ACOT13 may exert a protective role in ADPKD.", "claims": [{"id": "claim-method", "statement": "The differences between two groups were detected with an unpaired Student t-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39172111", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "The differences between two groups were detected with an unpaired Student t-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The dataset GSE7869 analyzed in this study was acquired from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39172111", "locator": "sections[15] \"Availability of data and materials\" paragraph 2", "quote": "The dataset GSE7869 analyzed in this study was acquired from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Compared to normal group, ACOT13 mRNA level was obviously reduced in renal cystic tissues and WT9-12 cells.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39172111", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Compared to normal group, ACOT13 mRNA level was obviously reduced in renal cystic tissues and WT9-12 cells."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Compared to normal group, ACOT13 mRNA level was obviously reduced in renal cystic tissues and WT9-12 cells.", "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:39172111"], "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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CONCLUSIONS: Collectively,", "tion and trigger mitochondrial-mediated cell apoptosis, suggesting that ACOT13 may exert a protecti"], "order_basis": "paper_text_order:115", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["evel in ADPKD cells (WT9-12) was verified by RT-qPCR. The effects of ACOT13 on WT9-12 cell growth", "l in ADPKD cells (WT9-12) was verified by RT-qPCR. The effects of ACOT13 on WT9-12 cell growth"], "order_basis": "paper_text_order:751", "id": "assay:2"}, {"role": "data_generation", "definition_id": "flow_cytometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["th were evaluated using the EdU staining and flow cytometry assays. RESULTS: Compared to normal group, A"], "order_basis": "paper_text_order:846", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.85, "evidence": ["MATERIALS AND METHODS Cell culture and transfection HK-2 (CL-0109, Procell) and ADPKD cell line"], "order_basis": "paper_text_order:1911", "id": "assay:4"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["cell line WT9-12 (CRL-2833, ATCC) cells were cultured in DMEM (PM150210, Procell) supplemented with 1", "a containing the lentivirus, cells were then cultured in fresh DMEM containing 10% FBS for indicated"], "order_basis": "paper_text_order:1997", "id": "assay:5"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The differences between two groups were detected with an unpaired Student t-test."], "order_basis": "consumes_earlier_output", "id": "assay:6"}]}