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However, the molecular mechanisms of effects of Cd on ECs remain poorly understood. Notch signaling pathway abnormalities have been implicated in ECs disruption. The present study aims to investigate the effect of low Cd concentrations on the Notch signaling pathway in ECs. Mice were treated with low concentration of Cd (2.28\u2009mg\/kg), and tissues were collected for examination of mRNA and protein levels of Notch pathway components and VE\u2010cadherin, a major junctional protein in ECs. We found that Cd treatment increases expression of NICD1, Hes1, Hey1, Hey2 and decreases expression of VE\u2010cadherin in brain and kidney tissues. In vitro, a low concentration of Cd (1\u2009\u03bcM) also induces increase expression of NICD1, Hes1, Hey1, Hey2, and decrease expression of VE\u2010cadherin in human umbilical vein endothelial cells (HUVECs). Low concentration of Cd increased the permeability of HUVECs. We also found that Notch signaling negatively regulates the expression of VE\u2010cadherin. In addition, DAPT, a Notch pathway inhibitor, prevents Cd\u2010induced reduction in VE\u2010cadherin expression in HUVECs. In summary, these findings revealed that Cd exposure decreases VE\u2010cadherin expression through activation of the Notch signaling pathway.<\/jats:p>","DOI":"10.1002\/jbt.70115","type":"journal-article","created":{"date-parts":[[2025,1,12]],"date-time":"2025-01-12T16:54:52Z","timestamp":1736700892000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cadmium Reduces VE\u2010Cadherin Expression in Endothelial Cells Through Activation of the Notch Signaling Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Yuanqing","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Respiratory and Intensive Care Unit, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital Shandong Institute of Respiratory Diseases Jinan China"},{"name":"Laboratory of Translational Medicine in Microvascular Regulation, Medical Research Center,The First 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