{
  "abstract": "Background: Ventilator-induced lung injury (VILI) is a major iatrogenic complication of mechanical ventilation, in which dysregulated inflammation, particularly macrophage-driven response, amplifies pulmonary damage. Although bone morphogenetic protein (BMP) signaling exhibits context-dependent effects in pulmonary disorders, whether specific BMP receptors (BMPRs) regulate macrophage function during VILI remains unknown.\n\nMethods: Mice subjected to mechanical ventilation were randomly divided into Control (intubation without ventilation), LVT (low tidal volume), and HVT (high tidal volume) groups. HVT-exposed mice received intratracheal administration of exogenous BMP4 or the BMP type I receptor antagonist LDN193189. Lung injury severity was assessed by ultrasound, macroscopic scoring, wet/dry ratio, and histopathology. Macrophage accumulation, M1/M2 polarization, interstitial-to-alveolar macrophage (IM/AM) ratio, and BMP receptor expression were evaluated. Transcriptomic profiling was performed to identify differentially expressed genes and enriched pathways. In vitro, gain- and loss-of-function experiments (overexpression and knockdown of BMPRIB) were conducted in RAW264.7 macrophages to assess cytokine/chemokine production, migration, and MAPK pathway activation. The p38 inhibitor SB202190 was used to probe downstream signaling.\n\nResults: Compared with Control and LVT groups, HVT induced time-dependent macrophage accumulation, skewed M1/M2 polarization, and a progressive elevation of the IM/AM ratio. Strikingly, HVT selectively upregulated BMPRIB in lung macrophages, while downregulating BMPRII and leaving BMPRIA unchanged. Intratracheal BMP4 exacerbated these effects, whereas LDN193189 reversed BMP4-induced macrophage accumulation, M1 polarization, IM/AM elevation, and suppressed activation of ERK, JNK, p38, and p65 signaling. Transcriptomic analysis revealed that BMP4 enriched MAPK and inflammation-related pathways, with LDN193189 co-treatment partially reversing this enrichment. In BMP4-stimulated RAW264.7 macrophages, BMPRIB overexpression enhanced, whereas BMPRIB knockdown attenuated, cytokine/chemokine production and migration. Pharmacological p38 inhibition (SB202190) abrogated BMP4-induced pro-inflammatory effects in macrophages.\n\nConclusions: HVT-induced BMPRIB upregulation in lung macrophages allows BMP4 to activate BMPRIB-dependent p38/NF-κB p65 axis as a key mediator of macrophage-driven inflammation in VILI Targeting the BMPRIB-dependent p38/NF-κB axis may represent a novel therapeutic strategy.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anesthesiology, The Second Xiangya Hospital, Central South University",
    "Hunan Province Center for Clinical Anesthesia and Anesthesiology, Research Institute of Central South University"
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jing Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Qi Sun"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lijuan Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Junmei Xu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lin Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bg22570f4v44s.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1947415",
  "fulltext_url": "https://europepmc.org/articles/PMC13680878",
  "id": "bg22570f4v44s",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1947415/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": [
    [
      "openalex",
      "2740|Respiratory Support and Mechanisms"
    ]
  ],
  "openalex": "W7220655918",
  "pdf_url": "https://europepmc.org/articles/PMC13680878?pdf=render",
  "pmcid": "PMC13680878",
  "pmid": "42903280",
  "published": "2026-10-06",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/bg22570f4v44s.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1947415",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1947415/full"
    },
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42903280",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42903280"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Macrophage BMPRIB mediates p38-dependent inflammatory reprogramming and chemotaxis during ventilator-induced lung injury",
  "title_text": "Macrophage BMPRIB mediates p38-dependent inflammatory reprogramming and chemotaxis during ventilator-induced lung injury",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/bg22570f4v44s",
  "venue": "Frontiers in Immunology",
  "versions": []
}