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Cd exposure has been elucidated to cause dysfunction of the glomerular filtration barrier (GFB). However, the underlying mechanism remains unclear. C57BL\/6J male mice were administered with 2.28\u2009mg\/kg cadmium chloride (CdCl<jats:sub>2<\/jats:sub>) dissolved in distilled water by oral gavage for 14\u2009days. The expression of SDC4 in the kidney tissues was detected. Human renal glomerular endothelial cells (HRGECs) were exposed to varying concentrations of CdCl<jats:sub>2<\/jats:sub> for 24\u2009h. The mRNA levels of SDC4, along with matrix metalloproteinase (MMP)\u20102 and 9, were analyzed by quantitative PCR. Additionally, the protein expression levels of SDC4, MMP\u20102\/9, and both total and phosphorylated forms of Smad2\/3 (P\u2010Smad2\/3) were detected by western blot. The extravasation rate of fluorescein isothiocyanate\u2013dextran through the Transwell was used to evaluate the permeability of HRGECs. SB431542 was used as an inhibitor of transforming growth factor (TGF)\u2010\u03b2 signaling pathway to further investigate the role of TGF\u2010\u03b2. Cd reduced SDC4 expression in both mouse kidney tissues and HRGECs. In addition, Cd exposure increased permeability and upregulated P\u2010Smad2\/3 levels in HRGECs. SB431542 treatment inhibited the phosphorylation of Smad2\/3, Cd\u2010induced SDC4 downregulation, and hyperpermeability. MMP\u20102\/9 levels increased by Cd exposure was also blocked by SB431542, demonstrating the involvement of TGF\u2010\u03b2\/Smad pathway in low\u2010dose Cd\u2010induced SDC4 reduction in HRGECs. Given that SDC4 is an essential component of glycocalyx, protection or repair of endothelial glycocalyx is a potential strategy for preventing or treating kidney diseases associated with environmental Cd exposure.<\/jats:p>","DOI":"10.1002\/jat.4592","type":"journal-article","created":{"date-parts":[[2024,2,24]],"date-time":"2024-02-24T00:25:28Z","timestamp":1708734328000},"page":"908-918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Low dose cadmium inhibits syndecan\u20104 expression in glycocalyx of glomerular endothelial cells"],"prefix":"10.1002","volume":"44","author":[{"given":"Xianli","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital  Jinan China"},{"name":"Institute of Microvascular Medicine, Medical Research Center The First Affiliated Hospital of 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