PIEZO1 Mediates Apoptosis of Endothelial Cells via Enhancing HMGA2 Expression Under Simulated Microgravity

Wang, Yuan; Wang, Ruonan; Qin, Xiaodong; Pan, Yikai; Li, Chengfei; Sun, Xiqing

doi:10.3390/ijms27031425

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PIEZO1 Mediates Apoptosis of Endothelial Cells via Enhancing HMGA2 Expression Under Simulated Microgravity

by

Yuan Wang

^†,

Ruonan Wang

^†,

Xiaodong Qin

,

Yikai Pan

,

Chengfei Li

^* and

Xiqing Sun

^*

Department of Aerospace Medical Training, School of Aerospace Medicine, Air Force Medical University, Xi’an 710032, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2026, 27(3), 1425; https://doi.org/10.3390/ijms27031425

Submission received: 24 December 2025 / Revised: 21 January 2026 / Accepted: 27 January 2026 / Published: 30 January 2026

(This article belongs to the Section Physical Chemistry and Chemical Physics)

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Abstract

Exposure to microgravity results in cardiovascular deconditioning, with endothelial cell apoptosis recognized as a pivotal initiating event. However, the mechanosensitive mechanisms underlying this process remain poorly understood. Here, we demonstrate that the expression of mechanosensitive ion channel protein PIEZO1 is upregulated in human umbilical vein endothelial cells (HUVECs) under simulated microgravity. Functional studies revealed that PIEZO1 activation promotes endothelial apoptosis under simulated microgravity conditions. Proteomic analysis following PIEZO1 knockdown revealed extensive alterations in biological processes associated with apoptosis. Furthermore, we found that PIEZO1 activation triggers calcium influx, leading to elevated expression of the HMGA2. Moreover, we identify that PIEZO1 activation induces calcium influx, which subsequently elevates the expression of HMGA2. The knockdown of HMGA2 significantly mitigated microgravity-induced endothelial apoptosis, indicating its role in PIEZO1-mediated apoptosis. These findings reveal a novel PIEZO1–Ca²⁺–HMGA2 axis critical for microgravity-induced endothelial apoptosis, providing mechanistic insight into cardiovascular adaptation to spaceflight and potential therapeutic targets for countermeasure development.

Keywords: simulated microgravity; PIEZO1; HMGA2; Ca²⁺; apoptosis

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MDPI and ACS Style

Wang, Y.; Wang, R.; Qin, X.; Pan, Y.; Li, C.; Sun, X. PIEZO1 Mediates Apoptosis of Endothelial Cells via Enhancing HMGA2 Expression Under Simulated Microgravity. Int. J. Mol. Sci. 2026, 27, 1425. https://doi.org/10.3390/ijms27031425

AMA Style

Wang Y, Wang R, Qin X, Pan Y, Li C, Sun X. PIEZO1 Mediates Apoptosis of Endothelial Cells via Enhancing HMGA2 Expression Under Simulated Microgravity. International Journal of Molecular Sciences. 2026; 27(3):1425. https://doi.org/10.3390/ijms27031425

Chicago/Turabian Style

Wang, Yuan, Ruonan Wang, Xiaodong Qin, Yikai Pan, Chengfei Li, and Xiqing Sun. 2026. "PIEZO1 Mediates Apoptosis of Endothelial Cells via Enhancing HMGA2 Expression Under Simulated Microgravity" International Journal of Molecular Sciences 27, no. 3: 1425. https://doi.org/10.3390/ijms27031425

APA Style

Wang, Y., Wang, R., Qin, X., Pan, Y., Li, C., & Sun, X. (2026). PIEZO1 Mediates Apoptosis of Endothelial Cells via Enhancing HMGA2 Expression Under Simulated Microgravity. International Journal of Molecular Sciences, 27(3), 1425. https://doi.org/10.3390/ijms27031425

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PIEZO1 Mediates Apoptosis of Endothelial Cells via Enhancing HMGA2 Expression Under Simulated Microgravity

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