KDM3A knockdown regulates COMP, LOX, COL8A1 and ACOT1 genes in myocardial fibrosis.

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Major focus of our study was to identify crucial genes involved in the pathological remodeling of the heart caused by pressure overload. We utilized various in-silico tools to analyze and interpret microarray data obtained from the Gene Expression Omnibus (GEO) database (GSE120739), including GEO2R analysis, Metascape analysis, WebGestalt analysis, and IPA (Ingenuity pathway analysis). Our findings indicate that certain genes, including Cartilage Oligomeric Matrix Protein (COMP), collagen type VIII alpha 1 chain (COL8A1) and Lysyl Oxidase (LOX) under the influence caused by knockdown of KDM3A, were down regulated by the extracellular matrix pathway. Moreover, genes, such as Acyl-CoA Thioesterase 1 (ACOT1) were up regulated by the fatty acid metabolism pathway. Overexpression of lysine-specific demethylase 3A (KDM3A) leads to the up regulation of fibrosis-related genes COMP, COL8A1, and LOX and the down regulation of ACOT1, result in enhanced fibrosis and heart failure. Our results suggest that COMP, COL8A1, LOX, and ACOT1 warrant further investigation in the development of cardiac fibrosis and as potential biomarkers for causing heart failure.", "claims": [{"id": "claim-method", "statement": "Thus, over-representation analysis (ORA) and gene set enrichment analysis (GSEA) indicated that KDM3A controls extracellular matrix biology and metabolism pathways, triggering fibrosis and enhancing ECM gene expression.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38854759", "locator": "sections[1] \"Background:\" paragraph 3", "quote": "Thus, over-representation analysis (ORA) and gene set enrichment analysis (GSEA) indicated that KDM3A controls extracellular matrix biology and metabolism pathways, triggering fibrosis and enhancing ECM gene expression."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Gene expression microarray data from the four left ventricles of mouse heart samples were collected from the Gene Expression Omnibus (GEO) database (accession number GSE120739).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38854759", "locator": "sections[3] \"Data source:\" paragraph 2", "quote": "Gene expression microarray data from the four left ventricles of mouse heart samples were collected from the Gene Expression Omnibus (GEO) database (accession number GSE120739)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Overexpression of KDM3A upregulates the fibrosis-related genes COMP, COL8A1, and LOX and downregulates ACOT1, resulting in enhanced fibrosis and heart failure.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38854759", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Overexpression of lysine-specific demethylase 3A (KDM3A) leads to the up regulation of fibrosis-related genes COMP, COL8A1, and LOX and the down regulation of ACOT1, result in enhanced fibrosis and heart failure."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Overexpression of KDM3A upregulates the fibrosis-related genes COMP, COL8A1, and LOX and downregulates ACOT1, resulting in enhanced fibrosis and heart failure.", "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:38854759"], "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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