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在生理和病理生理条件下在体内绘制细胞细胞 pH

Shuwei Zhang¹, Xiaoxin Hu¹, Bowen Zhang¹

¹Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China; Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China; Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai, China; Key Laboratory of Neuroregeneration of Shanghai Universities, School of Medicine, Tongji University, Shanghai, China; Stem Cell Research Center, School of Medicine, Tongji University, Shanghai, China.

The Journal of biological chemistry

|August 30, 2025

概括

研究人员使用转基因小鼠开发了一种新方法来测量细胞pH值. 这项技术揭示了细胞类型和糖尿病和癌症等疾病的显著pH变化.

科学领域:

细胞生物学
生理学
生物化学

背景情况:

细胞 pH (pHc) 对细胞功能至关重要,但在单细胞分辨率下进行体内测量是具有挑战性的.
在生理或病理生理变化期间,了解特定细胞类型的动态pHc反应是难以捉摸的.
Smad5是一种具有pH依赖核出口的蛋白质,具有作为pHc指标的潜力.

研究的目的:

建立一个转基因小鼠模型用于细胞pHc的定量体内测量.
在各种细胞类型和组织中绘制细胞pHc异质性.
根据生理和病理生理条件研究pHc的动态.

主要方法:

构成EGFP-Smad5表达的转基因小鼠作为pHc报告系统的开发.
报告小鼠的主要细胞类型的pHc定量映射.
评估细胞类型特定的pHc稳定性的急性系统酸化和化挑战.
在与2型糖尿病和瘤相关的病态微环境中分析pHc.

主要成果:

证明了eGFP-Smad5转基因小鼠在体内pHc报告器应用中的有用性.
在单个细胞类型和邻近组织细胞之间显示出显著的pHc异质性.
确定了不同的pHc稳定和pHc敏感细胞类型.
在2型糖尿病和瘤微环境中观察到特定细胞类型的响应性或适应性pHc变化.

结论:

在体内测绘细胞pHc的新且以前无法实现的方法.
突出了pHc在疾病发病,进展和细胞可塑性的病理生理相关性.
提供了在生理和病理条件下细胞pHc的动态性质的见解.

关键词:

没有.细胞质 pH 核细胞质分布病理生理学生理学

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