title: Phenotypic expression of ADAMTS13 in glomerular endothelial cells.
abstract: BACKGROUND
  ADAMTS13 is the physiological von Willebrand factor (VWF)-cleaving protease. The aim of this study was to examine ADAMTS13 expression in kidneys from ADAMTS13 wild-type (Adamts13⁺/⁺) and deficient (Adamts13⁻/⁻) mice and to investigate the expression pattern and bioactivity in human glomerular endothelial cells.
  
  
  RESULTS
  Immunohistochemistry was performed on kidney sections from ADAMTS13 wild-type and ADAMTS13-deficient mice. Phenotypic differences were examined by ultramorphology. ADAMTS13 expression in human glomerular endothelial cells and dermal microvascular endothelial cells was investigated by real-time PCR, flow cytometry, immunofluorescence and immunoblotting. VWF cleavage was demonstrated by multimer structure analysis and immunoblotting. ADAMTS13 was demonstrated in glomerular endothelial cells in Adamts13⁺/⁺ mice but no staining was visible in tissue from Adamts13⁻/⁻ mice. Thickening of glomerular capillaries with platelet deposition on the vessel wall was detected in Adamts13⁻/⁻ mice. ADAMTS13 mRNA and protein were detected in both human endothelial cells and the protease was secreted. ADAMTS13 activity was demonstrated in glomerular endothelial cells as cleavage of VWF.
  
  
  CONCLUSIONS
  Glomerular endothelial cells express and secrete ADAMTS13. The proteolytic activity could have a protective effect preventing deposition of platelets along capillary lumina under the conditions of high shear stress present in glomerular capillaries.
authors: Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.
authors: Ramesh
authors: R
authors: Tati
authors: Ann-Charlotte
authors: AC
authors: Kristoffersson
authors: Anne-Lie
authors: AL
authors: Ståhl
authors: Matthias
authors: M
authors: Mörgelin
authors: David
authors: D
authors: Motto
authors: Simon
authors: S
authors: Satchell
authors: Peter
authors: P
authors: Mathieson
authors: Minola
authors: M
authors: Manea-Hedström
authors: Diana
authors: D
authors: Karpman
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002196:Capillaries / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D006801:Humans; D007678:Kidney Glomerulus / Q000098:blood supply / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008666:Metalloendopeptidases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism
chemical_list: D003470:Culture Media; D012333:RNA, Messenger; D014841:von Willebrand Factor; D051722:ADAM Proteins; C502939:ADAMTS13 protein, mouse; D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human