Dentin matrix protein 1 correlates with the severity of hemorrhagic fever with renal syndrome and promotes hyper-permeability of endothelial cells infected by Hantaan virus |
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Authors: | Dongsha Shi Yanying Dong Pengfei Dai Juan Gao Jingjing Yin Ming Xie |
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Affiliation: | 1. Department of Pathogenic Biology and Immunology, School of Basic Medical Sciences, Xi''an Jiaotong University Health Science Center, Xi''an, Shaanxi, China;2. Clinical Laboratory, Tianjin Medical University General Hospital, Tianjin, China;3. Clinical Laboratory, The Second Affiliated Hospital of Xi''an Jiaotong University, Xi''an, Shaanxi, China;4. Department of Ophthalmology, Xi''an No. 4 Hospital, Xi''an, Shaanxi, China;5. Clinical Laboratory, Xi''an Gaoxin Hospital, Xi''an, Shaanxi, China |
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Abstract: | Hantaviruses are the major causative agents of hemorrhagic fever with renal syndrome (HFRS) in humans, which is characterized by increased capillary permeability. Dentin matrix protein 1 (DMP1) has been shown to degrade components of the basal membrane and interendothelial junctions via matrix metalloproteinase-9. To study the changes of serum DMP1 in HFRS, we determined the concentration of DMP1 using sandwich enzyme-linked immunosorbent assay. We found that serum DMP1 concentrations increased significantly, and reached peak value during the oliguric phase and in the critical group in HFRS patients. Moreover, serum DMP1 concentrations were closely related to blood urea nitrogen, creatinine, cystatin C, and vascular endothelial growth factor (VEGF). We further explored the role of DMP1 in HTNV-infected human umbilical vein endothelial cells (HUVECs) model. Data from immunocytochemistry showed that VEGF and tumor necrosis factor-α (TNF-α) promoted the expression of DMP1 on HTNV-infected HUVECs. Results from transwell assays demonstrated that the permeability of HUVECs increased significantly after HTNV infection with the addition of DMP1, VEGF, and TNF-α. This study suggests that elevated DMP1 concentrations may be associated with disease stage, severity, and the degree of acute kidney injury. DMP1 is involved in the regulation of capillary permeability in HFRS caused by hantavirus infection. |
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Keywords: | Corresponding author. School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, No.76 Yanta West Road, Xi'an, Shaanxi 710061, China. Fax: +86 29 82655730. Hemorrhagic fever with renal syndrome Hantavirus Dentin matrix protein 1 Vascular endothelial growth factor Tumor necrosis factor-α Hyper-permeability |
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