ACTN2, regulated by PRDM9, affects the growth and inflammation of vascular smooth muscle cells by interacting with PDLIM1 in intracranial aneurysms.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40881324", "kind": "science-record", "revision": 4, "content_hash": "sha256:d1b4a31c6c6e79ab7f9ec95ddc26d9896ed3f7ff03da2f9fb786467889573332", "created_at": "2026-11-01T20:30:59Z", "updated_at": "2026-11-01T22:57:07Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "ACTN2, regulated by PRDM9, affects the growth and inflammation of vascular smooth muscle cells by interacting with PDLIM1 in intracranial aneurysms.", "doi": "10.3389/fnmol.2025.1606973", "pmid": "40881324", "authors": ["Guangxu Zhang", "Jinbing Zhao", "Zhiqiang Yu", "Hongyi Liu"], "journal": "Frontiers in molecular neuroscience", "year": 2025, "abstract": "Background: The occurrence of aneurysms is closely related to the growth and inflammatory response of vascular smooth muscle cells (VSMCs). The regulatory mechanism of ACTN2 in intracranial aneurysms (IA) has not yet been fully elucidated. This study aims to reveal the role of the PRDM9-ACTN2-PDLIM1 axis in the progression of aneurysms and its impact on VSMCs.\nMethods: By integrating GEO datasets (GSE54083, GSE75436) and protein-protein interaction network analysis, ACTN2 was identified as a key gene. Techniques such as shRNA/overexpression, tissue staining, immunofluorescence, ELISA, and Western blot were used to analyze the effects of ACTN2 on VSMC proliferation, apoptosis, inflammation, and the Hippo pathway. The transcriptional regulation of ACTN2 by PRDM9 was validated through ChIP-qPCR, and the role of the PRDM9-H3K4me3-ACTN2 axis was explored using CRISPR-Cas9 experiments. PDLIM1 was screened as an interaction partner of ACTN2, and its role was verified through functional rescue experiments.\nResults: α-actinin-2 (ACTN2) was significantly downregulated in IA tissues. Its knockdown exacerbated vascular wall damage, VSMC apoptosis, and the release of inflammatory factors by inhibiting the Hippo pathway. PRDM9 promoted ACTN2 transcription through H3K4me3 modification, and its low expression led to ACTN2 suppression, driving VSMC proliferation inhibition and promoting apoptosis and inflammation. PDLIM1 interacted with ACTN2, and its overexpression reversed the effects of ACTN2 knockdown, which depended on the Hippo-YAP signaling pathway.\nConclusion: This study reveals that PRDM9 regulates ACTN2 expression through epigenetic modifications and interacts with PDLIM1 to mediate VSMC function and aneurysm progression. The study provides a theoretical basis for clinical intervention.", "claims": [{"id": "claim-method", "statement": "The limma package was used for differential expression analysis, and significantly differentially expressed genes were screened (|log2FC| > 1, p < 0.05).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40881324", "locator": "sections[3] \"Data acquisition and differential gene analysis\" paragraph 3", "quote": "The limma package was used for differential expression analysis, and significantly differentially expressed genes were screened (|log2FC| > 1, p < 0.05)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The protein-protein interaction data used in this study were obtained from the STRING database (https://string-db.org/). All data were processed and presented in accordance with the terms of use and citation guidelines of the STRING database. 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Its knockdown exacerbated vascular wall damage, VSMC apopt", "overexpression reversed the effects of ACTN2 knockdown, which depended on the Hippo-YAP signaling p", "PRDM9-H3K4me3-ACTN2 axis was explored using CRISPR-Cas9 experiments. PDLIM1 was screened as an", "identified as a key gene. Techniques such as shRNA/overexpression, tissue staining, immunofluor"], "order_basis": "paper_text_order:630", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ch as shRNA/overexpression, tissue staining, immunofluorescence, ELISA, and Western blot were used to analyz"], "order_basis": "paper_text_order:669", "id": "assay:2"}, {"role": "data_generation", "definition_id": "elisa", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ession, tissue staining, immunofluorescence, ELISA, and Western blot were used to analyze the e"], "order_basis": "paper_text_order:689", "id": "assay:3"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["sue staining, immunofluorescence, ELISA, and Western blot were used to analyze the effects of ACTN2 on"], "order_basis": "paper_text_order:700", "id": "assay:4"}, {"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": ["the effects of ACTN2 on VSMC proliferation, apoptosis, inflammation, and the Hippo pathway. The tr", "kdown exacerbated vascular wall damage, VSMC apoptosis, and the release of inflammatory factors by", "VSMC proliferation inhibition and promoting apoptosis and inflammation. PDLIM1 interacted with ACT"], "order_basis": "paper_text_order:779", "id": "assay:5"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["of ACTN2 by PRDM9 was validated through ChIP-qPCR, and the role of the PRDM9-H3K4me3-ACTN2 axi"], "order_basis": "paper_text_order:902", "id": "assay:6"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["d., [SCXK (SU) 2022-0006]. Upon arrival, the rats were acclimatized to the laboratory environment f", "lysis. Animal experiments The Sprague-Dawley rats used in this study were obtained from SiPeiF", "d., [SCXK (SU) 2022-0006]. Upon arrival, the rats were acclimatized to the laboratory environm", "virus was injected via the tail vein. If the rats exhibited mild hemiplegia symptoms (such as"], "order_basis": "paper_text_order:3008", "id": "assay:7"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["P-H116, Wuhan, Hubei, China). 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