miR-450a-2-3p targets ERK(1/2) to ameliorate ISO-induced cardiac fibrosis in mice.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39160527", "kind": "science-record", "revision": 4, "content_hash": "sha256:9957ce57de1e931ac0cc85e0ddce46264110eced94d3a067b65cc8550dec7620", "created_at": "2026-11-01T20:29:17Z", "updated_at": "2026-11-01T22:55:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "miR-450a-2-3p targets ERK(1/2) to ameliorate ISO-induced cardiac fibrosis in mice.", "doi": "10.1186/s12263-024-00753-6", "pmid": "39160527", "authors": ["Langsha Liu", "Fanyan Luo"], "journal": "Genes & nutrition", "year": 2024, "abstract": "OBJECTIVE: Cardiac fibrosis is an important contributor to atrial fibrillation (AF). Our aim was to identify biomarkers for AF using bioinformatics methods and explore the regulatory mechanism of miR-450a-2-3p in cardiac fibrosis in mice.\nMETHODS: Two datasets, GSE115574 and GSE79768, were obtained from the Gene Expression Omnibus (GEO) database and subsequently merged for further analysis. Differential gene expression analysis was performed to identify differentially expressed genes (DEGs) and miR-450a-2-3p-related differentially expressed genes (MRDEGs). To investigate the underlying mechanism of cardiac fibrosis, a mouse model was established by treating mice with isoproterenol (ISO) and the miR-450a-2-3p agomir.\nRESULTS: A total of 127 DEGs and 31 MRDEGs were identified and subjected to Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the functions and pathways involved in AF. In the animal model, histological analysis using HE and Masson staining, as well as quantification of the collagen volume fraction (CVF), was performed. The increased expression of α-smooth muscle actin (α-SMA), collagen type I (COL1), collagen type III (COL3), and extracellular signal-regulated kinase 1/2 (ERK(1/2)) at both the transcriptional and translational levels indicated the significant development of myocardial fibrosis in mice induced with isoproterenol (ISO). In addition, the cross-sectional area of cardiomyocytes and the expression of atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) were increased in the ISO group compared with the control group. However, after overexpression of the miR-450a-2-3p agomir through caudal vein injection, there was a notable improvement in cardiac morphology in the treated group. The expression levels of α-SMA, COL1, COL3, ERK(1/2), NPPA, and NPPB were also significantly decreased.\nCONCLUSION: Our study reveals the mechanistic connection between ISO-induced myocardial fibrosis and the miR-450a-2-3p/ERK(1/2) signaling pathway, highlighting its role in the development of cardiac fibrosis. Modulating miR-450a-2-3p expression and inhibiting ERK(1/2) activation are promising approaches for therapeutic intervention in patients with AF.", "claims": [{"id": "claim-method", "statement": "In the merged expression matrix, 126 differentially expressed genes (DEGs), namely, 50 upregulated genes and 76 downregulated genes, were identified using the \"limma\" R package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39160527", "locator": "sections[11] \"Screening for DEGs in AF\" paragraph 2", "quote": "In the merged expression matrix, 126 differentially expressed genes (DEGs), namely, 50 upregulated genes and 76 downregulated genes, were identified using the \"limma\" R package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39160527", "locator": "sections[23] \"notes\" paragraph 1", "quote": "The datasets used or analyzed during the current study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Our study reveals the mechanistic connection between ISO-induced myocardial fibrosis and the miR-450a-2-3p/ERK(1/2) signaling pathway, highlighting its role in the development of cardiac fibrosis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39160527", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Our study reveals the mechanistic connection between ISO-induced myocardial fibrosis and the miR-450a-2-3p/ERK(1/2) signaling pathway, highlighting its role in the development of cardiac fibrosis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Our study reveals the mechanistic connection between ISO-induced myocardial fibrosis and the miR-450a-2-3p/ERK(1/2) signaling pathway, highlighting its role in the development of cardiac 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:39160527"], "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": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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