Intracellular pH affects mitochondrial homeostasis in cultured human corneal endothelial cells prepared for cell injection therapy.
Intracellular pH affects mitochondrial homeostasis in cultured human corneal endothelial cells prepared for cell injection therapy.
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DOI：
10.1038/s41598-022-10176-1
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发表时间：
2022-04-15
影响因子：
4.6
通讯作者：
Hamuro, Junji
中科院分区：
文献类型：
--
作者：
Deguchi, Hideto;Yamashita, Tomoko;Hiramoto, Nao;Otsuki, Yohei;Mukai, Atsushi;Ueno, Morio;Sotozono, Chie;Kinoshita, Shigeru;Hamuro, Junji
本研究旨在揭示细胞注射治疗完全分化培养细胞的临床疗效的机制。分析培养的人角膜内皮细胞(CECs)亚群(SP)上离子转运体的极化表达。测量了分化细胞比例不同的两个CEC SP之间的细胞内pH(Phi)，并研究了其与线粒体呼吸动态平衡的关系。并探讨了选择性抑制剂或siRNA对离子转运体的抑制作用。Na+/K+-ATPase、Aquaporin 1、SLC4A11、NBCe1、NHE1和ZO-1在分化的SP中均有选择性表达，但在细胞状态转换的SP中几乎为零。我们还证实，CEC SPS的PHI通过抑制或siRNA转染调节这些离子转运体的表达，从而影响它们的线粒体呼吸。离子转运体和水转运体可能参与了分化SPS的phi和线粒体动态平衡的维持，这可能与完整的屏障功能相结合，有助于有效的水外流。两种SPS细胞内pH的差异归因于特定离子转运体的表达谱和线粒体功能的不同，这可能与SPS在细胞注射治疗中的疗效有关。
This study aimed to uncover the mechanism responsible for the clinical efficacy of cell injection therapy with fully differentiated cultured cells. Analysis of polarized expression of ion transporters on cultured human corneal endothelial cells (CECs) subpopulations (SPs) was performed. The intracellular pH (pHi) between two CEC SPs, distinct in the proportion of differentiated cells, was measured, and the association with mitochondrial respiration homeostasis was investigated. The effects of the ion transporter inhibition by their selective inhibitors or siRNA transfection were also explored. Na+/K+-ATPase, Aquaporin 1, SLC4A11, NBCe1, NHE1 as transporters, and ZO-1, were all selectively expressed in differentiated SPs, but were almost null in the cell-state-transitioned SPs. We also confirmed that the pHi of CEC SPs affected their mitochondrial respiration by modulating the expression of these ion transporters via inhibitors or siRNA transfection. Ion and water transporters might participate in the maintenance of pHi and mitochondria homeostasis in differentiated SPs, which may contribute, combined with integral barrier functions, to efficient water efflux. The differences in intracellular pH between the two SPs is attributed to variations in the expression profile of specific ion transporters and mitochondrial functions, which may associate with the efficacy of the SPs in cell injection therapy.
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