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流体剪切压力诱导的大胆蛋白贩运的变化增强了近端管细胞的内细胞容量

Emily M Lackner¹, Isabella A Cowan¹, Kimberly R Long¹

¹Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.

Frontiers in physiology

|July 1, 2024

概括

液体剪切应力通过增加大素和素的表达和贩运来增强近接管细胞内细胞酶. 这个模型有助于理解蛋白质回收和毒药物吸收.

科学领域:

细胞生物学细胞生物学
脏生理学脏生理学
生物物理学的生物物理.

背景情况:

靠近管 (PT) 细胞利用顶端内细胞结合 (apical endocytosis) 通过巨氨酸和氨酸受体恢复蛋白质.
这些受体还调节毒药物的吸收,造成损伤的风险.
在流体剪切应力 (FSS) 下的子 (OK) 细胞在体内比静态培养更好地模仿PT细胞功能.

研究的目的:

为了确定驱动PT细胞中高容量内细胞通路的因素.
为了比较FSS培养和静态培养OK细胞之间的内细胞功能和受体动态.
评估FSS培养OK细胞作为毒药物吸收模型的实用性.

主要方法:

在FSS和静态条件下对OK细胞进行生化和形态分析.
量化大林和林的表达和专蛋白的吸收.
数学模型的巨贩运的动态.
对毒药物吸收机制的评估.

主要成果:

与静态细胞相比,FSS培养的OK细胞的白蛋白吸收率高出5倍.
在FSS培养的细胞中,巨和素的表达显著增加.
数学建模揭示了FSS培养细胞中的加速巨毒素贩运,解释了尽管表面受体动态发生了变化,但吸收增加.
在体内,FSS培养的细胞更好地复制了毒药物吸收机制.

结论:

液体切割应力通过调节受体表达和贩运,显著增强近接管细胞内细胞能力.
用FSS培养的OK细胞为研究蛋白质再吸收和毒性提供了卓越的体外模型.
这种模式对制定预防药物诱导损伤的策略有影响.

关键词:

细胞内源性细胞分裂 (endocytosis) 发生在细胞内.这是一种 gentamicin 药物.数学模型是一个数学模型.梅加琳·梅加林是什么意思剪切压力的压力.

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