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Peer-reviewedCC BY-NC-ND 4.0Molecular Medicine Reports

Piezo1 knockdown alleviates high-altitude cerebral edema by improving brain microvascular endothelial cell tight junctions via blocking the calcium influx-mediated Calpain-1 activity

  • Taijian Cao1
  • Zhicheng Xiang2
  • Yangyang Zhao3
  • Drolma Gomchok2
  • Haifeng Ma4
  • Shiwang Li2
  • Dahai Cao2
  • Chunqing Yang2
  • Qiang Zhang5
5 affiliations
  1. 1Department of Spinal Surgery, Qinghai University Affiliated Hospital, College of Clinical Medicine, Qinghai University, Xining, Qinghai 810001, P.R. China
  2. 2College of Clinical Medicine, Qinghai University, Xining, Qinghai 810001, P.R. China
  3. 3Department of Dermatology and Plastic Surgery, Qinghai University Affiliated Hospital, College of Clinical Medicine, Qinghai University, Xining, Qinghai 810001, P.R. China
  4. 4Department of Neurosurgery, Qinghai Provincial People's Hospital, Xining, Qinghai 810006, P.R. China
  5. 5Department of Neurosurgery, High-Altitude Disease Clinical Medical Research Center of Qinghai Province, Qinghai Provincial People's Hospital, Xining, Qinghai 810006, P.R. China
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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.

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Cite

BibTeXRIS
BibTeX
@article{cao2026piezo1,
  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}},
  author = {Taijian Cao and Zhicheng Xiang and Yangyang Zhao and Drolma Gomchok and Haifeng Ma and Shiwang Li and Dahai Cao and Chunqing Yang and Qiang Zhang},
  journal = {Molecular Medicine Reports},
  year = {2026},
  month = oct,
  doi = {10.3892/mmr.2026.14042},
  url = {https://doi.org/10.3892/mmr.2026.14042},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Piezo1 knockdown alleviates high-altitude cerebral edema by improving brain microvascular endothelial cell tight junctions via blocking the calcium influx-mediated Calpain-1 activity
AU  - Taijian Cao
AU  - Zhicheng Xiang
AU  - Yangyang Zhao
AU  - Drolma Gomchok
AU  - Haifeng Ma
AU  - Shiwang Li
AU  - Dahai Cao
AU  - Chunqing Yang
AU  - Qiang Zhang
PY  - 2026
DA  - 2026/10/13
JO  - Molecular Medicine Reports
DO  - 10.3892/mmr.2026.14042
UR  - https://doi.org/10.3892/mmr.2026.14042
AB  - 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.
SN  - 1791-2997
SN  - 1791-3004
ER  -