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Intracellular calcium response of primary cilia of tubular cells to modulated shear stress under oxidative stress.
Biomicrofluidics ( IF 2.6 ) Pub Date : 2020-07-02 , DOI: 10.1063/5.0010737
Masatomo Chikamori 1 , Hiroshi Kimura , Reiko Inagi 2 , Jing Zhou 3 , Masaomi Nangaku 2 , Teruo Fujii 1
Affiliation  

Primary cilia of tubular cells are sensory organelles. Bending of the primary cilia with shear stress from urinary flow results in the elevation of intracellular calcium levels and activation of signaling pathways that maintain kidney function. Elongation of primary cilia is reported to occur due to oxidative stress, which is a major cause of ischemia-reperfusion injury and is accompanied by decreased kidney function. However, in the context of diminished kidney function, this elongation is yet to be investigated. In this study, we developed a new microfluidic device to monitor changes in the intracellular calcium levels while modulating shear stress on the cilia under different degrees of oxidative stress. The microfluidic device was designed to expose even shear stress in the observed area while supplying drugs in four different stepwise concentrations. The results showed that primary cilia were elongated by hydrogen peroxide, which induces oxidative stress. It was also observed that the elongated primary cilia were more sensitive to shear stress than those with normal morphology. This microfluidic device could, thus, be useful in the analysis of the morphology of the primary cilia, under low perfusion conditions.

中文翻译:

肾小管细胞初级纤毛对氧化应激下的剪切应力的细胞内钙反应。

肾小管细胞的初级纤毛是感觉细胞器。尿流产生的切应力使原发纤毛弯曲,导致细胞内钙水平升高和激活维持肾脏功能的信号通路。据报道,原发纤毛的伸长是由于氧化应激引起的,氧化应激是缺血再灌注损伤的主要原因,并伴有肾功能下降。但是,在肾功能减弱的情况下,这种伸长尚待研究。在这项研究中,我们开发了一种新的微流控装置,以监测细胞内钙水平的变化,同时在不同程度的氧化胁迫下调节纤毛上的剪切应力。该微流控设备设计为在提供四个不同的逐步浓度的药物的同时,在观察区域内暴露出均匀的剪切应力。结果表明,原纤毛被过氧化氢拉长,引起氧化应激。还观察到,伸长的初级纤毛比具有正常形态的纤毛对剪切应力更敏感。因此,在低灌注条件下,这种微流体装置可用于分析初级纤毛的形态。
更新日期:2020-09-01
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