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通过囊泡介导的apoptotic senolytics需要机械负荷

Zhulin Xue^1,2, Yexiang Jiang², Bowen Meng²

¹Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology & National Center for Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China.

|September 6, 2024

概括

机械卸载通过降低Piezo1.1的调节来减少apoptotic囊泡 (apoVs). 输注apoVs可以挽救这种效应,维持apoptotic稳态,并消除衰老细胞.

科学领域:

机械生物学机械生物学
细胞生物学细胞生物学
生物医学工程生物医学工程

背景情况:

机械力对于细胞外囊泡 (EV) 功能至关重要,包括生物发生和释放.
机械力对瘤囊泡 (apoV) 生产的特定影响仍然在很大程度上未被探索.
了解这种关系对于开发新的治疗策略至关重要.

研究的目的:

调查机械卸载在调节apoV生产中的作用及其后果.
确定apoVs在抵消机械卸载诱导的细胞功能障碍方面的治疗潜力.
阐明涉及Piezo1和信号的潜在分子机制.

主要方法:

利用后肢卸载 (HU) 鼠标模型来模拟机械卸载,并分析骨髓EVs.
使用HU小鼠和细胞微重力模型评估细胞亡抵抗和衰老表型.
采用微计算机断层扫描,组织化学,免疫组织化学和组织形态测量来评估apoV的治疗效果.
使用siRNA和化学处理进行了功能增益和丧失研究.

主要成果:

机械卸载导致细胞亡抵抗和衰老的表型,减少循环的apoVs.
确定了下调的Piezo1表达和减少的流作为关键机制.
对apoVs的全身输液挽救了Piezo1的表达和的流入,减轻了卸载诱导的影响.
在HU小鼠中,ApoV治疗逆转了细胞亡抵抗和衰老细胞积累.

结论:

机械力对于维持亡的恒常状态和清除衰老细胞至关重要.
介质干细胞衍生的apoVs显示出显著的治疗潜力.
在机械卸载的条件下,全身的apoV输液可以有效地挽救apoptotic抵抗并消除衰老细胞.

关键词:

灭症 (apoptosis) 是一种死亡的过程.它们是apoptotic囊泡.机械卸载机械卸载介质细胞干细胞介质细胞干细胞衰老细胞是衰老的细胞.

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