{
  "abstract": "High-altitude cerebral edema (HACE) is a life-threatening complication of acute high-altitude exposure, but effective treatment strategies remain limited. The influence of Piezo1 on the tight junctions of brain microvascular endothelial cells in HACE was examined to identify novel therapeutic interventions against HACE. A mouse model of HACE was established through exposure to a simulated high-altitude hypobaric hypoxia environment. Brain water content, Evans Blue staining, magnetic resonance imaging, hematoxylin and eosin staining, FITC-Dextran leakage assay and transmission electron microscopy were utilized to evaluate the impact of Piezo1 on HACE. A cell model of HACE was created by subjecting bEnd.3 cells to high fluid shear stress (HFSS) and hypoxic conditions. The effects of Piezo1 and Calpain-1 on tight junction protein expression were assessed via western blot analysis. Mice with HACE exhibited increased brain water content, disrupted blood-brain barrier integrity, enhanced microvascular permeability, hippocampal and cortical damage and reduced expression of VE-cadherin, occludin, claudin-5 and ZO-1 proteins, alongside elevated Piezo1 and Calpain-1 activity in brain microvascular endothelial cells. Silencing of Piezo1 alleviated these HACE symptoms. bEnd.3 cells subjected to HFSS and hypoxia showed increased intracellular Ca2+, along with heightened Calpain-1 protein expression and activity, while levels of VE-cadherin, occludin, claudin-5 and ZO-1 proteins were diminished. Both Piezo1 silencing and Calpain-1 inhibition reversed these in vitro changes. Notably, Piezo1 silencing reduced Calpain-1 activity without significantly altering Calpain-1 protein levels. Piezo1 silencing may ameliorate HACE by enhancing tight junctions in brain microvascular endothelial cells through the suppression of calcium influx-mediated Calpain-1 activity. Thus, targeting Piezo1 expression may represent a promising therapeutic approach for HACE.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Spinal Surgery, Qinghai University Affiliated Hospital, College of Clinical Medicine, Qinghai University, Xining, Qinghai 810001, P.R. China",
    "College of Clinical Medicine, Qinghai University, Xining, Qinghai 810001, P.R. China",
    "Department of Dermatology and Plastic Surgery, Qinghai University Affiliated Hospital, College of Clinical Medicine, Qinghai University, Xining, Qinghai 810001, P.R. China",
    "Department of Neurosurgery, Qinghai Provincial People's Hospital, Xining, Qinghai 810006, P.R. China",
    "Department of Neurosurgery, High-Altitude Disease Clinical Medical Research Center of Qinghai Province, Qinghai Provincial People's Hospital, Xining, Qinghai 810006, P.R. China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Taijian Cao"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhicheng Xiang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yangyang Zhao"
    },
    {
      "affs": [
        1
      ],
      "name": "Drolma Gomchok"
    },
    {
      "affs": [
        3
      ],
      "name": "Haifeng Ma"
    },
    {
      "affs": [
        1
      ],
      "name": "Shiwang Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Dahai Cao"
    },
    {
      "affs": [
        1
      ],
      "name": "Chunqing Yang"
    },
    {
      "affs": [
        4
      ],
      "name": "Qiang Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2yf4107mqhvyn.bib",
  "cited_by": 0,
  "doi": "10.3892/mmr.2026.14042",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13697153/",
  "id": "2yf4107mqhvyn",
  "issns": [
    "1791-2997",
    "1791-3004"
  ],
  "landing_url": "https://doi.org/10.3892/mmr.2026.14042",
  "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",
      "Articles"
    ],
    [
      "openalex",
      "1311|High Altitude and Hypoxia"
    ]
  ],
  "openalex": "W7203528535",
  "pdf_url": "https://europepmc.org/articles/PMC13697153?pdf=render",
  "pmcid": "PMC13697153",
  "pmid": "42885283",
  "published": "2026-10-13",
  "publisher": "Spandidos Publications",
  "ris": "https://research.draconitic.com/paper/2yf4107mqhvyn.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:17Z",
      "native_id": "PMC13697153",
      "source": "pmc",
      "url": "https://doi.org/10.3892/mmr.2026.14042"
    },
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42885283",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42885283"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1311|High Altitude and Hypoxia",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Piezo1 knockdown alleviates high-altitude cerebral edema by improving brain microvascular endothelial cell tight junctions via blocking the calcium influx-mediated Calpain-1 activity",
  "title_text": "Piezo1 knockdown alleviates high-altitude cerebral edema by improving brain microvascular endothelial cell tight junctions via blocking the calcium influx-mediated Calpain-1 activity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:16Z",
  "url": "https://research.draconitic.com/paper/2yf4107mqhvyn",
  "venue": "Molecular Medicine Reports",
  "versions": []
}