ADAM10 is expressed in human podocytes and found in urinary vesicles of patients with glomerular kidney diseases.
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.
Gutwein
Paul
P
Pharmazentrum frankfurt/ZAFES, University Hospital Goethe University Frankfurt, Frankfurt am Main, Germany. p.gutwein@med.uni-frankfurt.de
Schramme
Anja
A
Abdel-Bakky
Mohamed Sadek
MS
Doberstein
Kai
K
Hauser
Ingeborg A
IA
Ludwig
Andreas
A
Altevogt
Peter
P
Gauer
Stefan
S
Hillmann
Anja
A
Weide
Thomas
T
Jespersen
Christine
C
Eberhardt
Wolfgang
W
Pfeilschifter
Josef
J
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
D008565:Membrane Proteins; D034741:RNA, Small Interfering; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human