{
  "abstract": "Background: Previous studies have confirmed the therapeutic potential of Astragaloside IV (AS-IV) in pulmonary fibrosis, yet the upstream regulatory mechanisms governing TGF-β1 stability, particularly involving proteolytic enzymes, are not fully understood. This study investigates the pivotal role of calpain-1 in modulating the HSP90/TGF-β1 signaling pathway, thereby elucidating the effects of AS-IV on bleomycin (BLM)-induced pulmonary fibrosis.\n\nMethods: Calpain-1 knockout (CAPN1 −/− ) and wild-type (WT) mice were used to establish pulmonary fibrosis models via intratracheal instillation of BLM. Both animal and cell models were administered varying doses of AS-IV for intervention. Inflammatory, oxidative stress, fibrotic, and epithelial-mesenchymal transition (EMT) markers were subsequently evaluated. Additionally, molecular docking, molecular dynamics simulations, and surface plasmon resonance (SPR) experiments were employed to assess the binding interactions between AS-IV and the calpain-1/HSP90/TGF-β1 axis.\n\nResults: The calpain-1/HSP90/TGF-β1 axis was significantly activated in BLM-induced pulmonary fibrosis mice. AS-IV ameliorated pulmonary fibrosis, EMT, oxidative stress, and inflammation while simultaneously suppressing this overactivated axis. Calpain-1 knockout inhibited HSP90 upregulation, attenuated TGF-β1/Smad2/3 activation, and reduced pulmonary fibrosis. In vivo experiments further confirmed the inhibitory effects of AS-IV and calpain-1 inhibition on lung epithelial cell injury and fibroblast proliferation. Notably, calpain-1 overexpression in MLE-12 cells abolished the protective effects of AS-IV against EMT, oxidative stress, and inflammation. Molecular docking, molecular dynamics simulations, and SPR experiments confirmed the direct binding between AS-IV and calpain-1, supporting its upstream regulatory role in this signaling axis.\n\nConclusion: AS-IV attenuates pulmonary fibrosis by targeting calpain-1 to disrupt the HSP90/TGF-β1 signaling axis. These findings identify calpain-1 as a novel therapeutic target and support AS-IV as a promising candidate for PF treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University",
    "The First Affiliated Hospital of Jinzhou Medical University",
    "The Third Affiliated Hospital of Jinzhou Medical University"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Silin Wei"
    },
    {
      "affs": [
        0
      ],
      "name": "Yu Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Bailin Tang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yang Yu"
    },
    {
      "affs": [
        1
      ],
      "name": "Nan Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Meili Lu"
    },
    {
      "affs": [
        2
      ],
      "name": "Lili Sun"
    },
    {
      "affs": [
        1
      ],
      "name": "Guijun Wang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/egnvzzdrx78v8.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1864914",
  "fulltext_url": "https://europepmc.org/articles/PMC13713264",
  "id": "egnvzzdrx78v8",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1864914/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2740|Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis"
    ]
  ],
  "openalex": "W7221808087",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1864914/pdf",
  "pmcid": "PMC13713264",
  "pmid": "42952476",
  "published": "2026-10-14",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/egnvzzdrx78v8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1864914",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1864914/full"
    },
    {
      "first_seen": "2026-10-31T00:20:34Z",
      "native_id": "MED:42952476",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42952476"
    },
    {
      "first_seen": "2026-10-31T12:23:50Z",
      "native_id": "PMC13713264",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fphar.2026.1864914"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "issn:1663-9812",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Blockade of the calpain-1/HSP90/TGF-β1 axis by Astragaloside IV ameliorates bleomycin-induced pulmonary fibrosis",
  "title_text": "Blockade of the calpain-1/HSP90/TGF-β1 axis by Astragaloside IV ameliorates bleomycin-induced pulmonary fibrosis",
  "type": "peer-reviewed",
  "updated_at": "2026-11-01T12:20:58Z",
  "url": "https://research.draconitic.com/paper/egnvzzdrx78v8",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}