{
  "abstract": "Introduction: Myocardial ischemia-reperfusion injury (MIRI) remains a significant challenge in cardiovascular medicine, and its molecular mechanisms are not yet fully elucidated.\n\nMethods: In the present study, integrated transcriptomic analysis combined with machine learning identified PMEPA1 as a key gene consistently downregulated in both rat models of MIRI and H9c2 cardiomyocytes subjected to ischemia –reperfusion injury. A series of in vivo and in vitro experiments, including gene overexpression and knockdown, cell viability and proliferation assays, flow cytometry, Western blot, co-immunoprecipitation, and immunofluorescence, were performed to investigate the role and underlying mechanism of PMEPA1 in MIRI.\n\nResults: Overexpression of PMEPA1 enhanced cardiomyocyte proliferation, reduced apoptosis, and inhibited activation of the TGF-β/SMAD signaling pathway. Further investigation revealed a direct interaction between PMEPA1 and the E3 ubiquitin ligase NEDD4. Both NEDD4 overexpression and PMEPA1 knockdown aggravated cardiomyocyte injury and increased activation of the TGF-β/SMAD pathway. Notably, the detrimental effects of NEDD4 overexpression were attenuated in the absence of PMEPA1, suggesting a PMEPA1-dependent mechanism.\n\nDiscussion: These findings highlight a novel NEDD4–PMEPA1 axis in the regulation of TGF-β/SMAD signaling during myocardial injury and provide new insights into potential molecular targets for the treatment of cardiovascular disease.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical University , ,",
    "Department of Pediatrics, Jinzhou Maternal and Child Hospital , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 3,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Weilong Zhong"
    },
    {
      "affs": [
        1
      ],
      "name": "Yanan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Baoze Qu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/35tkgnymtj4k2.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1881951",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668540/?tool=EBI",
  "id": "35tkgnymtj4k2",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13668540",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2734|Cardiac Ischemia and Reperfusion"
    ]
  ],
  "openalex": "W7215072988",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668540/pdf/?tool=EBI",
  "pmcid": "PMC13668540",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/35tkgnymtj4k2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13668540",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13668540"
    },
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1881951",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1881951/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "PMEPA1 attenuates myocardial ischemia-reperfusion injury via interaction with NEDD4 and involvement of the TGF-β/SMAD pathway",
  "title_text": "PMEPA1 attenuates myocardial ischemia-reperfusion injury via interaction with NEDD4 and involvement of the TGF-β/SMAD pathway",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/35tkgnymtj4k2",
  "venue": "Frontiers in pharmacology",
  "versions": []
}