Cadmium regulates von Willebrand factor and occludin expression in glomerular endothelial cells of mice in a TNF-α-dependent manner.

BACKGROUND: Cadmium (Cd) is an environmental pollutant that leads to nephrotoxicity. However, the mechanisms of Cd-induced glomerular injury have not been fully clarified. Von Willebrand factor (vWF) and occludin are important endothelial cell markers in renal vasculature. In this study, the effects of Cd on the vWF and occludin expression in mouse glomeruli was investigated. OBJECTIVES: The goal of this study was to analyze the expression of von Willebrand factor and occludin in glomerular endothelial cells of tumor necrosis factor-α(-/-) (TNF-α(-/-)) mice after treatment with Cd. MATERIAL AND METHODS: C57BL6/J wild-type (WT) mice and TNF-α(-/-) mice (n = 6) were treated with Cd, and the kidney tissues were collected. The expression of von Willebrand factor and occludin was detected by using quantitative real-time PCR, immunofluorescence, and immunohistochemistry. In vitro, Human umbilical vascular endothelial cells (HUVECs) were used to examine the regulatory role of TNF-α on expression of von Willebrand factor and occludin. RESULTS: We found that Cd significantly increases mRNA and protein expressions of von Willebrand factor and occludin in TNF-α(-/-) mice, but not in WT mice. In vitro, Cd significantly increased mRNA and protein expression of von Willebrand factor and occludin in HUVECs with TNF-α small interfering RNA (siRNA) transfection. CONCLUSIONS: These results suggest that TNF-α acts to balance homeostasis of glomerular endothelium after Cd treatments.