Hyperosmolar environment and intestinal epithelial cells: impact on mitochondrial oxygen consumption, proliferation, and barrier function in vitro
Hyperosmolar environment and intestinal epithelial cells: impact on mitochondrial oxygen consumption, proliferation, and barrier function in vitro
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DOI：
10.1038/s41598-019-47851-9
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发表时间：
2019-08-06
影响因子：
4.6
通讯作者：
Blachier, Francois
中科院分区：
文献类型：
--
作者：
Grauso, Marta;Lan, Annaig;Blachier, Francois
本研究的目的是阐明在体外短期（2小时）和长期（24小时）的影响，高渗介质（500和680 mOsm/L）对肠上皮细胞使用人结肠细胞Caco-2细胞系模型。我们发现，与正常渗透压（336 mOsm/L）相比，高渗环境减缓了细胞增殖，而不会诱导细胞脱离或坏死。这与细胞线粒体耗氧量的瞬时减少、质子泄漏的增加和细胞内ATP含量的减少有关。Caco-2单层的屏障功能也受到短暂影响，因为测量到细胞旁顶部至基底的渗透性增加和电解质渗透性改变，允许跨上皮渗透压差部分平衡。此外，高渗应激诱导促炎细胞因子IL-8的分泌。通过测定参与能量代谢、紧密连接形成、电解质渗透性和细胞内信号传导的基因的表达，根据高渗胁迫的强度和持续时间，发生了不同的反应模式。这些数据强调了增加的管腔渗透压对肠上皮更新和屏障功能的潜在影响，并指出了一些细胞对管腔高渗环境的适应能力。
The aim of the present study was to elucidate the in vitro short-term (2-h) and longer-term (24-h) effects of hyperosmolar media (500 and 680 mOsm/L) on intestinal epithelial cells using the human colonocyte Caco-2 cell line model. We found that a hyperosmolar environment slowed down cell proliferation compared to normal osmolarity (336 mOsm/L) without inducing cell detachment or necrosis. This was associated with a transient reduction of cell mitochondrial oxygen consumption, increase in proton leak, and decrease in intracellular ATP content. The barrier function of Caco-2 monolayers was also transiently affected since increased paracellular apical-to-basal permeability and modified electrolyte permeability were measured, allowing partial equilibration of the trans-epithelial osmotic difference. In addition, hyperosmotic stress induced secretion of the pro-inflammatory cytokine IL-8. By measuring expression of genes involved in energy metabolism, tight junction forming, electrolyte permeability and intracellular signaling, different response patterns to hyperosmotic stress occurred depending on its intensity and duration. These data highlight the potential impact of increased luminal osmolarity on the intestinal epithelium renewal and barrier function and point out some cellular adaptive capacities towards luminal hyperosmolar environment.