High-Throughput Sequencing Data Reveal an Antiangiogenic Role of HNF4A-Mediated CACNA1A/VEGFA Axis in Proliferative Diabetic Retinopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37342032", "kind": "science-record", "revision": 4, "content_hash": "sha256:5df25c9d8384b04d7e5d99252676b185f63a5d6a774df6b507dcf9fedd5c7dcf", "created_at": "2026-11-01T19:02:04Z", "updated_at": "2026-11-01T22:52:09Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "High-Throughput Sequencing Data Reveal an Antiangiogenic Role of HNF4A-Mediated CACNA1A/VEGFA Axis in Proliferative Diabetic Retinopathy.", "doi": "10.1167/iovs.64.7.32", "pmid": "37342032", "authors": ["Yuan Yin", "Shuai Wu", "Lingzhi Niu", "Shiwei Huang"], "journal": "Investigative ophthalmology & visual science", "year": 2023, "abstract": "Purpose: Proliferative diabetic retinopathy (PDR) is characterized by retinal new vessel formation, pointing to the importance of the antiangiogenic treatment in PDR. Hepatocyte nuclear factor 4A (HNF4A) has been highlighted to inhibit vascular endothelial growth factor (VEGF)-stimulated in vitro angiogenesis. Therefore, this study aims to elucidate the potential antiangiogenic mechanisms of HNF4A in PDR.\nMethods: PDR-related high-throughput sequencing datasets (GSE94019, GSE102485, and GSE191210) were obtained from the Gene Expression Omnibus (GEO) database, followed by the screening of differentially expressed genes (DEGs). The protein-protein interaction (PPI) network of the candidate DEGs was constructed based on gene set enrichment analysis (GSEA) data and Search Tool for the Retrieval of Interacting Genes (STRING) data. In addition, the key genes and pathways related to angiogenesis were screened by functional enrichment analysis. Furthermore, human retinal microvascular cells were used for further in vitro validation.\nResults: Four key genes (CACNA1A, CACNA1E, PDE1B, and CHRM3) related to PDR were identified in the grey module. CACNA1A affected angiogenesis in PDR by regulating vascular endothelial growth factor A (VEGFA) expression. Furthermore, HNF4A participated in angiogenesis in PDR by activating CACNA1A. In vitro experiments further identified that inhibition of HNF4A reduced CACNA1A expression and increased VEGFA expression, thus promoting angiogenesis in PDR.\nConclusions: In conclusion, the obtained findings suggest that antiangiogenic HNF4A activates the CACNA1A/VEGFA axis in PDR. Our work provides new insights into the angiogenic mechanism of PDR and offers potential targets for translational applications.", "claims": [{"id": "claim-method", "statement": "DEGs between healthy controls and PDR samples were screened through the “limma” package in R software, with |logFC| > 1 and P value < 0.05 as the threshold.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37342032", "locator": "sections[7] \"Differential Analysis of Sequencing Data\" paragraph 2", "quote": "DEGs between healthy controls and PDR samples were screened through the “limma” package in R software, with |logFC| > 1 and P value < 0.05 as the threshold."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data Availability Statement: The data that supports the findings of this study are available on request from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37342032", "locator": "sections[26] \"Acknowledgments\" paragraph 3", "quote": "Data Availability Statement: The data that supports the findings of this study are available on request from the corresponding author upon reasonable request."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "", "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:37342032"], "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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