title: ADAM10 is expressed in human podocytes and found in urinary vesicles of patients with glomerular kidney diseases.
abstract: BACKGROUND
  The importance of the Notch signaling in the development of glomerular diseases has been recently described. Therefore we analyzed in podocytes the expression and activity of ADAM10, one important component of the Notch signaling complex.
  
  
  METHODS
  By Western blot, immunofluorescence and immunohistochemistry analysis we characterized the expression of ADAM10 in human podocytes, human urine and human renal tissue.
  
  
  RESULTS
  We present evidence, that differentiated human podocytes possessed increased amounts of mature ADAM10 and released elevated levels of L1 adhesion molecule, one well known substrate of ADAM10. By using specific siRNA and metalloproteinase inhibitors we demonstrate that ADAM10 is involved in the cleavage of L1 in human podocytes. Injury of podocytes enhanced the ADAM10 mediated cleavage of L1. In addition, we detected ADAM10 in urinary podocytes from patients with kidney diseases and in tissue sections of normal human kidney. Finally, we found elevated levels of ADAM10 in urinary vesicles of patients with glomerular kidney diseases.
  
  
  CONCLUSIONS
  The activity of ADAM10 in human podocytes may play an important role in the development of glomerular kidney diseases.
authors.affiliation: Pharmazentrum frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main, Germany. p.gutwein@med.uni-frankfurt.de
authors.forename: Paul
authors.initials: P
authors.lastname: Gutwein
authors.forename: Anja
authors.initials: A
authors.lastname: Schramme
authors.forename: Mohamed Sadek
authors.initials: MS
authors.lastname: Abdel-Bakky
authors.forename: Kai
authors.initials: K
authors.lastname: Doberstein
authors.forename: Ingeborg A
authors.initials: IA
authors.lastname: Hauser
authors.forename: Andreas
authors.initials: A
authors.lastname: Ludwig
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
authors.forename: Stefan
authors.initials: S
authors.lastname: Gauer
authors.forename: Anja
authors.initials: A
authors.lastname: Hillmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Weide
authors.forename: Christine
authors.initials: C
authors.lastname: Jespersen
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Eberhardt
authors.forename: Josef
authors.initials: J
authors.lastname: Pfeilschifter
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D000072197:ADAM10 Protein; D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D002460:Cell Line; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000652:urine; D008875:Middle Aged; D050199:Podocytes / Q000201:enzymology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014556:Urine / Q000166:cytology
chemical_list: D008565:Membrane Proteins; D034741:RNA, Small Interfering; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human