{
  "abstract": "Aims: Pulmonary hypertension (PH), a severe vascular disorder, is closely associated with chronic inflammatory states and oxidative stress. Myeloid differentiation protein 2 (MD2), a key co-receptor of Toll-like receptor 4 (TLR4), is well established in mediating various inflammation-driven pathologies. However, its role in pulmonary hypertension and its potential involvement in oxidative stress regulation remain unclear. Methods and results: MD2 expression was upregulated in both PH patients and murine PH models. Genetic or pharmacological inhibition of MD2 improved hemodynamic parameters, attenuated pulmonary vascular remodeling, and reduced right ventricular hypertrophy. MD2 inhibition significantly reduced mitochondrial oxidative stress in vivo and in vitro . Mechanistic studies demonstrated that suppression of the membrane protein MD2 activated intracellular AMP-activated protein kinase (AMPK) signaling, leading to enhanced peroxisome proliferator-activated receptor γ (PPARγ) activity. PPARγ, in turn, suppressed nuclear transcription of NADPH oxidase 4 (NOX4), resulting in a marked reduction in mitochondrial oxidative stress. Conclusion: This study indicates that MD2 may act as an upstream regulator of mitochondrial oxidative stress in PH. Inhibition of MD2 attenuates pulmonary hypertension through activation of the AMPK/PPARγ axis, which suppresses NOX4 mediated mitochondrial oxidative stress. Targeting MD2 may represent a novel therapeutic strategy for PH.",
  "abstract_shown": true,
  "affiliations": [
    "Pulmonary Division, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou Key Laboratory of Interdisciplinary and Translational Medicine, Wenzhou Key Laboratory of Heart and Lung, Wenzhou, Zhejiang, 325035, China; Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China",
    "Wenzhou Medical University, Wenzhou, Zhejiang, 325000, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jun Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengyu Chai"
    },
    {
      "affs": [
        0
      ],
      "name": "Yichen Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yaxin Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiuchun Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Congxuan Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Haofeng Pan"
    },
    {
      "affs": [
        0
      ],
      "name": "Chen Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Yizhu Yao"
    },
    {
      "affs": [
        1
      ],
      "name": "Yahan Yu"
    },
    {
      "affs": [
        1
      ],
      "name": "Juntao Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Dan Yao"
    },
    {
      "name": "Xiaoying Huang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4hzw9tyzfg5d0.bib",
  "cited_by": 0,
  "doi": "10.1016/j.redox.2026.104454",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2213231726004532",
  "id": "4hzw9tyzfg5d0",
  "issns": [
    "2213-2317"
  ],
  "landing_url": "https://doi.org/10.1016/j.redox.2026.104454",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Paper"
    ],
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "lcc",
      "R5-920"
    ],
    [
      "openalex",
      "2740|Pulmonary Hypertension Research and Treatments"
    ]
  ],
  "openalex": "W7223261074",
  "pdf_url": null,
  "pmcid": "PMC13722578",
  "pmid": "42925726",
  "published": "2026-10-23",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/4hzw9tyzfg5d0.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:47:17Z",
      "native_id": "168ca0e0461b4b57b18c2b60909f83c5",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.redox.2026.104454"
    },
    {
      "first_seen": "2026-11-04T12:21:22Z",
      "native_id": "PMC13722578",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.redox.2026.104454"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Redox biology and oxidative stress",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "lcc:QH301-705.5",
      "subfield": "general"
    },
    {
      "field": "medicine",
      "origin": "lcc:R5-920",
      "subfield": "general"
    }
  ],
  "title": "Inhibiting MD2 activates AMPK-dependent PPARγ/NOX4 signaling to attenuate mitochondrial oxidative stress and relieve pulmonary hypertension",
  "title_text": "Inhibiting MD2 activates AMPK-dependent PPARγ/NOX4 signaling to attenuate mitochondrial oxidative stress and relieve pulmonary hypertension",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:22Z",
  "url": "https://research.draconitic.com/paper/4hzw9tyzfg5d0",
  "venue": "Redox Biology",
  "versions": []
}