Upregulation of Intracellular Calcium by Piezo1 Activation Mediates UTMD-Activated ATP Release by Rat Erythrocytes

IF 2.8 3区医学 Q2 ACOUSTICS

Ultrasound in Medicine and Biology Pub Date : 2026-03-01 Epub Date: 2025-12-02 DOI:10.1016/j.ultrasmedbio.2025.11.002

Anna Xu , Qiong Zhu , Yanshuo Shi , Lei Gao , Zheng Liu , Yueheng Wang

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引用次数: 0

Abstract

Objective

Ultrasound Targeted Microbubble Destruction (UTMD) technology enhances microvascular blood perfusion, with adenosine triphosphate (ATP) release from red blood cells (RBCs) playing a crucial role. However, the precise mechanisms remain unclear. This study aimed to investigate the role of Piezo1 in regulating ATP release from RBCs by UTMD.

Methods

RBCs were collected from rats, and UTMD was carried out using a modified ultrasonic thrombolysis device with lipid-fluorine microbubbles. RBCs were treated with the Piezo1 activator Yoda1, the Piezo1 blocker GsMTx4 or the Pannexin1 (Panx1) blocker carbenoxolone, prior to UTMD. ATP release was assessed using a bioluminescence assay with an in vivo imaging system, and intracellular calcium (Ca²⁺) concentration was determined by laser confocal microscopy. Data-independent acquisition proteomic analysis was conducted to identify differential protein expression in the UTMD and Control groups.

Results

UTMD-induced Piezo1 activation promoted ATP release from RBCs by facilitating Ca²⁺ influx. Proteomic analysis highlighted differentially expressed proteins, including Dematin, Protein 4.1, Moesin and Myosin, suggesting their involvement in the process. Additionally, Panx1 likely contributed as a downstream regulator of activated Piezo1.

Conclusion

Our findings suggest that UTMD enhances ATP release from RBCs via a synergistic mechanism: Piezo1-mediated Ca²⁺ influx as the primary pathway, and non-Piezo1 pathways (including sonoporation) as complements. UTMD-induced Ca²⁺ influx is dominated by Piezo1-independent mechanisms. Panx1 acts as a key downstream effector. Although our results show Panx1 inhibition reduces ATP release, direct evidence of Piezo1-Panx1 interaction remains to be established. Proteomic data suggest cytoskeletal remodeling may play a role in this process. This knowledge may contribute to the development of new therapeutic strategies for improving microcirculatory perfusion.

查看原文本刊更多论文

Piezo1激活上调胞内钙介导utmd激活的大鼠红细胞ATP释放。

目的：超声靶向微泡破坏（UTMD）技术增强微血管血流灌注，红细胞（红细胞）释放三磷酸腺苷（ATP）起关键作用。然而，确切的机制仍不清楚。本研究旨在探讨Piezo1在通过UTMD调节红细胞ATP释放中的作用。方法：取大鼠红细胞，采用改良的脂氟微泡超声溶栓装置进行UTMD。在UTMD之前，用Piezo1激活剂Yoda1、Piezo1阻滞剂GsMTx4或Pannexin1 （Panx1）阻滞剂carbenoxolone处理红细胞。使用体内成像系统的生物发光法评估ATP释放，并通过激光共聚焦显微镜测定细胞内钙（Ca2+）浓度。进行数据独立获取蛋白质组学分析，以确定UTMD组和对照组的差异蛋白表达。结果：utmd诱导的Piezo1激活通过促进Ca2+内流促进红细胞ATP释放。蛋白质组学分析强调了差异表达蛋白，包括Dematin， Protein 4.1， Moesin和Myosin，表明它们参与了这一过程。此外，Panx1可能是活化Piezo1的下游调节因子。结论：我们的研究结果表明，UTMD通过协同机制增强红细胞的ATP释放：piezo1介导的Ca2+内流是主要途径，非piezo1途径（包括声共振）是补充途径。utmd诱导的Ca2+内流主要是由piezo1独立的机制。Panx1是一个关键的下游效应物。虽然我们的研究结果显示Panx1抑制减少ATP释放，但Piezo1-Panx1相互作用的直接证据仍有待建立。蛋白质组学数据表明，细胞骨架重塑可能在这一过程中发挥作用。这一知识可能有助于发展新的治疗策略，以改善微循环灌注。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Ultrasound in Medicine and Biology 医学-核医学

CiteScore

6.20

自引率

6.90%

发文量

325

审稿时长

70 days

期刊介绍： Ultrasound in Medicine and Biology is the official journal of the World Federation for Ultrasound in Medicine and Biology. The journal publishes original contributions that demonstrate a novel application of an existing ultrasound technology in clinical diagnostic, interventional and therapeutic applications, new and improved clinical techniques, the physics, engineering and technology of ultrasound in medicine and biology, and the interactions between ultrasound and biological systems, including bioeffects. Papers that simply utilize standard diagnostic ultrasound as a measuring tool will be considered out of scope. Extended critical reviews of subjects of contemporary interest in the field are also published, in addition to occasional editorial articles, clinical and technical notes, book reviews, letters to the editor and a calendar of forthcoming meetings. It is the aim of the journal fully to meet the information and publication requirements of the clinicians, scientists, engineers and other professionals who constitute the biomedical ultrasonic community.