Department of Pediatrics, DGSOM at UCLA, 10833 LeConte Ave., 12-383 MDCC, Los Angeles, CA 90095, USA.
VA GLAHS 11301 Wilshire Blvd, Bldg 113, Rm 324, Los Angeles, CA 90073, USA.
Biomolecules. 2024 Jun 28;14(7):772. doi: 10.3390/biom14070772.
is a highly prevalent human gastric pathogen that causes gastritis, ulcer disease, and gastric cancer. It is not yet fully understood how injures the gastric epithelium. The Na,K-ATPase, an essential transporter found in virtually all mammalian cells, has been shown to be important for maintaining the barrier function of lung and kidney epithelia. decreases levels of Na,K-ATPase in the plasma membrane of gastric epithelial cells, and the aim of this study was to demonstrate that this reduction led to gastric injury by impairing the epithelial barrier. Similar to infection, the inhibition of Na,K-ATPase with ouabain decreased transepithelial electrical resistance and increased paracellular permeability in cell monolayers of human gastric cultured cells, 2D human gastric organoids, and gastric epithelium isolated from gerbils. Similar effects were caused by a partial shRNA silencing of Na,K-ATPase in human gastric organoids. Both infection and ouabain exposure disrupted organization of adherens junctions in human gastric epithelia as demonstrated by E-cadherin immunofluorescence. Functional and structural impairment of epithelial integrity with a decrease in Na,K-ATPase amount or activity provides evidence that the -induced downregulation of Na,K-ATPase plays a role in the complex mechanism of gastric disease induced by the bacteria.
是一种高度流行的人类胃病原体，可引起胃炎、溃疡病和胃癌。目前尚不完全清楚如何损伤胃上皮。Na，K-ATPase 是一种几乎存在于所有哺乳动物细胞中的必需转运蛋白，已被证明对于维持肺和肾上皮的屏障功能很重要。减少胃上皮细胞质膜中的 Na，K-ATPase 水平，本研究旨在证明这种减少通过损害上皮屏障导致胃损伤。类似于感染，哇巴因抑制 Na，K-ATPase 会降低单层人胃培养细胞、2D 人胃类器官和来自沙鼠的胃上皮中的跨上皮电阻并增加旁细胞通透性。在人胃类器官中，Na，K-ATPase 的部分 shRNA 沉默也会引起类似的影响。感染和哇巴因暴露都会破坏人胃上皮细胞中黏着连接的组织，如 E-钙黏蛋白免疫荧光所示。上皮完整性的功能和结构受损，Na，K-ATPase 数量或活性减少，这表明细菌引起的胃疾病的复杂机制中，起作用。
