Shear Stress‐Stimulated Trafficking of Endothelial Piezo1 to Splenic Capsule Boosts Spleen Contraction and Exercise Endurance
4 affiliations
- 1Key Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine Fourth Military Medical University Xi'an China
- 2State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine Fourth Military Medical University Xi'an China
- 3Department of Ultrasound Medicine, Tangdu Hospital Fourth Military Medical University Xi'an China
- 4Department of Cardiovascular Medicine The First Affiliated Hospital of Xi'an Jiaotong University Xi'anChina
Abstract
Haemodynamic shear stress, sensed by vascular endothelial cells (ECs), is crucial for the functional integrity of ECs and the systemic benefits of exercise. Here, we observed that shear stress triggers the release of medium/large extracellular vesicles (m/lEVs), from ECs via activation of the mechanosensitive ion channel Piezo1. Endothelial Piezo1 activation induces Piezo1 translocation to the cell periphery, facilitating its trafficking from the vascular ECs to the smooth muscle cells in the splenic capsule. Within the splenic capsule, the translocated Piezo1 acts as a downstream effector of α1‐adrenergic receptor, boosting exercise‐induced spleen contraction and enhancing exercise endurance. Genetic or pharmacological inhibition of Piezo1 trafficking from ECs impaired spleen contraction during exercise and reduced exercise endurance in mice. Additionally, exercise‐induced m/lEV release contributes to safeguard endothelial function through modulating intracellular Piezo1 homeostasis. Furthermore, positive correlations between exercise‐induced increases in circulating Piezo1‐enriched m/lEVs and the degree of spleen contraction were also observed in human volunteers. These findings unveil a vasculo‐splenic axis during exercise, in which EC‐derived m/lEVs shuttle Piezo1 to maintain endothelial function and exercise endurance, highlighting a novel role of Piezo1 in inter‐organ communication.
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BibTeX
@article{lou2026shear,
title = {{Shear Stress‐Stimulated Trafficking of Endothelial Piezo1 to Splenic Capsule Boosts Spleen Contraction and Exercise Endurance}},
author = {Jing Lou and Mingzong Yang and Yang Hu and Xuyun Liu and Han Li and Zihang Feng and Yuxin Xi and Changyang Xing and Lijun Yuan and Jia Li and Shengpeng Wang and Feng Gao and Xing Zhang},
journal = {Journal of Extracellular Vesicles},
year = {2026},
month = oct,
doi = {10.1002/jev2.70375},
url = {https://doi.org/10.1002/jev2.70375},
note = {CC BY},
}
RIS
TY - JOUR
TI - Shear Stress‐Stimulated Trafficking of Endothelial Piezo1 to Splenic Capsule Boosts Spleen Contraction and Exercise Endurance
AU - Jing Lou
AU - Mingzong Yang
AU - Yang Hu
AU - Xuyun Liu
AU - Han Li
AU - Zihang Feng
AU - Yuxin Xi
AU - Changyang Xing
AU - Lijun Yuan
AU - Jia Li
AU - Shengpeng Wang
AU - Feng Gao
AU - Xing Zhang
PY - 2026
DA - 2026/10/26
JO - Journal of Extracellular Vesicles
DO - 10.1002/jev2.70375
UR - https://doi.org/10.1002/jev2.70375
AB - Haemodynamic shear stress, sensed by vascular endothelial cells (ECs), is crucial for the functional integrity of ECs and the systemic benefits of exercise. Here, we observed that shear stress triggers the release of medium/large extracellular vesicles (m/lEVs), from ECs via activation of the mechanosensitive ion channel Piezo1. Endothelial Piezo1 activation induces Piezo1 translocation to the cell periphery, facilitating its trafficking from the vascular ECs to the smooth muscle cells in the splenic capsule. Within the splenic capsule, the translocated Piezo1 acts as a downstream effector of α1‐adrenergic receptor, boosting exercise‐induced spleen contraction and enhancing exercise endurance. Genetic or pharmacological inhibition of Piezo1 trafficking from ECs impaired spleen contraction during exercise and reduced exercise endurance in mice. Additionally, exercise‐induced m/lEV release contributes to safeguard endothelial function through modulating intracellular Piezo1 homeostasis. Furthermore, positive correlations between exercise‐induced increases in circulating Piezo1‐enriched m/lEVs and the degree of spleen contraction were also observed in human volunteers. These findings unveil a vasculo‐splenic axis during exercise, in which EC‐derived m/lEVs shuttle Piezo1 to maintain endothelial function and exercise endurance, highlighting a novel role of Piezo1 in inter‐organ communication.
SN - 2001-3078
ER -