Osteopontin regulates right ventricular failure through integrin ανβ3/PERK/CHOP-dependent inflammatory and apoptotic pathways.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40396173", "kind": "science-record", "revision": 3, "content_hash": "sha256:75748a8544f8452f0393e7d4a3714b7d2c7680f2bb80034aa3ad52e090c3ef92", "created_at": "2026-11-01T20:30:32Z", "updated_at": "2026-11-01T22:14:05Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Osteopontin regulates right ventricular failure through integrin ανβ3/PERK/CHOP-dependent inflammatory and apoptotic pathways.", "doi": "10.3389/fimmu.2025.1569210", "pmid": "40396173", "authors": ["Xiaomei Yang", "Xuyang Wang", "Kai Li", "Qiming Deng", "Yonghao Hou", "Guangmin Xi", "Kangping Lu", "Zihua Liu", "Yu Bai", "Jianbo Wu", "Jingui Yu", "Peng Zhang"], "journal": "Frontiers in immunology", "year": 2025, "abstract": "Introduction: Right ventricular failure is a life-threatening condition commonly associated with obvious immune responses in its progression. This study aims to investigate the role of osteopontin (OPN) in right ventricular failure pathogenesis and evaluate its potential as a therapeutic target.\nMethods: This study adopted a multi-level design. First, immune-related differentially expressed genes (IRDEGs) were identified using the GEO database (GSE161473) and immune cell composition analysis via ImmuCellAI. A right ventricular failure (RVF) rat model was established, and Western blot, RT-qPCR, and immunohistochemical/immunofluorescence analyses were performed to assess OPN expression and inflammatory infiltration. In vitro, neonatal rat cardiomyocytes were treated with recombinant OPN to examine changes in endoplasmic reticulum stress markers, while the Integrin-ανβ3 inhibitor LM609 was used to delineate OPN's mechanism of action. Finally, in a clinical study, serum OPN levels were measured by ELISA and compared with NT-proBNP through correlation and Receiver Operating Characteristic (ROC) analyses.\nResults: We found that OPN triggered cardiomyocyte inflammatory responses by activating endoplasmic reticulum stress via the Integrin-ανβ3/PERK/CHOP pathway. OPN exhibited concentration-dependent effects on cardiomyocyte survival: at 2 μg/ml it showed protective effects through BCL-2 modulation, while higher concentrations promoted apoptosis. Importantly, serum OPN levels strongly correlated with NT-proBNP and disease severity in RVF patients.\nDiscussion: These findings identify OPN as a crucial mediator of RVF pathogenesis through the regulation of inflammatory and apoptotic pathways, establishing its potential as a promising therapeutic target.", "claims": [{"id": "claim-method", "statement": "Correlations were assessed using Pearson’s correlation coefficient.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40396173", "locator": "sections[16] \"Statistical analysis\" paragraph 2", "quote": "Correlations were assessed using Pearson’s correlation coefficient."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed for this study can be found in the Gene Expression Omnibus (GEO) database: GSE161473 and GSE120852.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40396173", "locator": "sections[30] \"Data availability statement\" paragraph 2", "quote": "The datasets analyzed for this study can be found in the Gene Expression Omnibus (GEO) database: GSE161473 and GSE120852."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Serum OPN levels strongly correlated with NT-proBNP and disease severity in RVF patients.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40396173", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Importantly, serum OPN levels strongly correlated with NT-proBNP and disease severity in RVF patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Serum OPN levels strongly correlated with NT-proBNP and disease severity in RVF patients.", "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:40396173"], "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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