{
  "abstract": "Ischemic skin flaps are highly susceptible to distal necrosis because of insufficient perfusion, oxidative stress, and dysregulated cell death. Here, we investigated the role of Hippo/YAP signaling in ischemic flap survival and identified its upstream regulatory mechanism. Hippo pathway inactivation, characterized by reduced MST1/2 and LATS1/2 phosphorylation and enhanced YAP nuclear localization, was preferentially associated with viable flap regions. Mechanistically, ischemia-induced HIF-1α upregulated miR-210-3p, which suppressed ephrin-A3 (EFNA3), weakened the EFNA3-YAP interaction, and promoted YAP nuclear translocation. Re-expression of EFNA3 partially reversed miR-210-3p-induced YAP activation and cytoprotection, confirming its functional involvement. Mechanistically, ischemia-induced HIF-1α increased miR-210-3p expression, which suppressed EFNA3 and facilitated YAP nuclear localization. EFNA3 re-expression partially reversed miR-210-3p-induced YAP activation, supporting its functional involvement. MiR-210-3p treatment was further associated with reduced oxidative injury, lipid peroxidation, mitochondrial dysfunction, and ferroptosis-related molecular alterations, together with improved perfusion and flap survival. In vivo, miR-210-3p improved local perfusion and flap survival. We further developed a virus-inspired biomimetic nanoparticle for miR-210-3p delivery, which achieved protective effects comparable to AAV-mediated delivery in vitro and in vivo. These findings identify the miR-210-3p-EFNA3-YAP axis as an important regulator of ischemic tissue adaptation and provide a non-viral miRNA delivery strategy for ischemic flap repair.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopaedics, Yongkang First People's Hospital of Wenzhou Medical University, Jinhua, 321300, Zhejiang, China.",
    "Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.",
    "Department of Wound healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.",
    "Department of Radiology, Ruian Hospital Affiliated to Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.",
    "The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.",
    "The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. jiangwb919@wmu.edu.cn.",
    "Department of Orthopaedics, Yongkang First People's Hospital of Wenzhou Medical University, Jinhua, 321300, Zhejiang, China. xjian@wmu.edu.cn.",
    "Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. xjian@wmu.edu.cn.",
    "Department of Wound healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. xjian@wmu.edu.cn.",
    "Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. chmlzh@wmu.edu.cn.",
    "Department of Wound healing, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China. chmlzh@wmu.edu.cn.",
    "Department of Orthopaedics, Yongkang First People's Hospital of Wenzhou Medical University, Jinhua, 321300, Zhejiang, China. m13566758233@163.com."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Jie Xu"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Xiuxiu Zhuang"
    },
    {
      "affs": [
        1
      ],
      "name": "Zichang Wu"
    },
    {
      "affs": [
        1
      ],
      "name": "Fuyi Yan"
    },
    {
      "affs": [
        3
      ],
      "name": "Deen Shi"
    },
    {
      "affs": [
        1
      ],
      "name": "Fan Ye"
    },
    {
      "affs": [
        1
      ],
      "name": "Ruihua Ding"
    },
    {
      "affs": [
        1
      ],
      "name": "Qi Gao"
    },
    {
      "affs": [
        1
      ],
      "name": "Qimin Yao"
    },
    {
      "affs": [
        4
      ],
      "name": "Yiying Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaoyu Dong"
    },
    {
      "affs": [
        1
      ],
      "name": "Fan Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Binbiao Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiangwei Xu"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongfei Tong"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanzhi Yao"
    },
    {
      "affs": [
        5
      ],
      "name": "Wenbing Jiang"
    },
    {
      "affs": [
        6,
        7,
        8
      ],
      "name": "Jian Xiao"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Zhenglin Li"
    },
    {
      "affs": [
        11
      ],
      "name": "Wei Chen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/cpvfqdczntpgy.bib",
  "cited_by": 0,
  "doi": "10.1186/s12951-026-04833-0",
  "fulltext_url": "https://europepmc.org/articles/PMC13689359",
  "id": "cpvfqdczntpgy",
  "issns": [
    "1477-3155"
  ],
  "landing_url": "https://europepmc.org/article/MED/42907899",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R855-855.5"
    ],
    [
      "lcc",
      "TP248.13-248.65"
    ],
    [
      "openalex",
      "1307|Hippo pathway signaling and YAP/TAZ"
    ]
  ],
  "openalex": "W7171204960",
  "pdf_url": "https://europepmc.org/articles/PMC13689359?pdf=render",
  "pmcid": "PMC13689359",
  "pmid": "42907899",
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/cpvfqdczntpgy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:59Z",
      "native_id": "MED:42907899",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42907899"
    },
    {
      "first_seen": "2026-10-30T13:46:29Z",
      "native_id": "f4c9168db5f44d58add3d6674da5fc18",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s12951-026-04833-0"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Hippo pathway signaling and YAP/TAZ",
      "subfield": "cell-biology"
    }
  ],
  "title": "Identification of the miR-210-3p-EFNA3-YAP axis and its targeted modulation via biomimetic supramolecular nanoparticles to promote ischemic flap survival.",
  "title_text": "Identification of the miR-210-3p-EFNA3-YAP axis and its targeted modulation via biomimetic supramolecular nanoparticles to promote ischemic flap survival.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:46:29Z",
  "url": "https://research.draconitic.com/paper/cpvfqdczntpgy",
  "venue": "Journal of nanobiotechnology",
  "versions": []
}