title: Short-term, low-dose cadmium exposure induces hyperpermeability in human renal glomerular endothelial cells.
abstract: The kidney is the principal organ targeted by exposure to cadmium (Cd), a well-known toxic metal. Even at a low level, Cd damages glomerular filtration. However, little is known about the effects of Cd on the glomerular endothelium, which performs the filtration function and directly interacts with Cd in blood plasma. In this study, we cultured human renal glomerular endothelial cells (HRGECs) in the presence of serum with treatment of a short term (1 h) and low concentration (1 μm) of Cd, which mimics the pattern of glomerular endothelium exposure to Cd in vivo. We found that this short-term, low-dose Cd exposure does not induce cytotoxicity, but increases permeability in HRGECs monolayers and redistributes adherens junction proteins vascular endothelial-cadherin and β-catenin. Though short-term, low-dose Cd exposure activates all three major mitogen activated protein kinases, only the inhibitor of p38 mitogen activated protein kinase partially prevents Cd-induced hyperpermeability in HRGECs. Our data indicate that the presence of Cd in blood circulation might directly disrupt the glomerular endothelial cell barrier and contribute to the development of clinical symptoms of glomerular diseases.
authors.affiliation: Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Li
authors.affiliation: Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Fengyun
authors.initials: F
authors.lastname: Dong
authors.affiliation: Department of Nephrology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of Nephrology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Linna
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Yan
authors.affiliation: Department of Cardiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Hesheng
authors.initials: H
authors.lastname: Hu
authors.affiliation: Miami Mice Research Corp., Toronto, Ontario, Canada.
authors.forename: Corrinne G
authors.initials: CG
authors.lastname: Lobe
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yi
authors.affiliation: Department of Biology, Trent University, Peterborough, Ontario, Canada.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Kapron
authors.affiliation: Laboratory of Microvascular Medicine, Medical Research Center, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Liu
mesh_terms: D002104:Cadmium / Q000097:blood / Q000633:toxicity*; D049108:Cell Enlargement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects*; D042783:Endothelial Cells / Q000187:drug effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects*
chemical_list: D002104:Cadmium
keywords: VE-cadherin; cadmium; p38 MAPK; permeability; renal glomerular endothelial cells