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Podocytes express ADAMTS13 in normal renal cortex and in patients with thrombotic thrombocytopenic purpura

Manea Hedström, Minola LU ; Kristoffersson, Ann-Charlotte LU ; Schneppenheim, Reinhard; Saleem, Moin A.; Mathieson, Peter W.; Mörgelin, Matthias LU ; Björk, Peter LU ; Holmberg, Lars LU and Karpman, Diana LU (2007) In British Journal of Haematology 138(5). p.651-662
Abstract
Congenital thrombotic thrombocytopenic purpura (TTP) is associated with ADAMTS13 mutations. The major site of ADAMTS13 synthesis is the liver. Expression in other tissues, and in TTP, has not been shown. In this study, ADAMTS13 protein expression was investigated in normal kidney and in renal tissue from two TTP patients, with a compound heterozygous mutation (P353L and P457L) and a homozygous mutation (4143insA). Real-time polymerase chain reaction demonstrated ADAMTS13 mRNA in normal kidney. ADAMTS13 was detected in the glomeruli and tubuli of normal and TTP kidney using anti-ADAMTS13 antibodies. In the glomeruli, expression was localised to podocytes (as demonstrated by counterstaining with two podocyte markers) and endothelium. Similar... (More)
Congenital thrombotic thrombocytopenic purpura (TTP) is associated with ADAMTS13 mutations. The major site of ADAMTS13 synthesis is the liver. Expression in other tissues, and in TTP, has not been shown. In this study, ADAMTS13 protein expression was investigated in normal kidney and in renal tissue from two TTP patients, with a compound heterozygous mutation (P353L and P457L) and a homozygous mutation (4143insA). Real-time polymerase chain reaction demonstrated ADAMTS13 mRNA in normal kidney. ADAMTS13 was detected in the glomeruli and tubuli of normal and TTP kidney using anti-ADAMTS13 antibodies. In the glomeruli, expression was localised to podocytes (as demonstrated by counterstaining with two podocyte markers) and endothelium. Similar distribution was detected in the TTP kidneys. Electron microscopy detected ADAMTS13 in podocytes, endothelium and glomerular basement membrane. Cultured human podocytes expressed ADAMTS13 mRNA and protein, and podocyte lysate exhibited von Willebrand factor-cleaving activity. Mutation expression studies of the P353L and P457L mutations showed partially impaired secretion and lower activity of the secreted mutants. Impaired secretion has previously been shown for the 4143insA mutation. Podocyte-derived ADAMTS13 may offer local protection in the high-shear microcirculation of the glomerulus. The mutations in the two TTP patients studied enabled protein expression in the podocytes but affected protease secretion. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
thrombotic thrombocytopenic purpura, endothelial cells, podocytes, kidney, ADAMTS13
in
British Journal of Haematology
volume
138
issue
5
pages
651 - 662
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000248591100011
  • scopus:34547636148
ISSN
0007-1048
DOI
10.1111/j.1365-2141.2007.06694.x
language
English
LU publication?
yes
id
957e18eb-cd4e-4650-9a12-2541e4ae0c76 (old id 686764)
date added to LUP
2007-12-13 12:39:48
date last changed
2017-10-01 03:46:02
@article{957e18eb-cd4e-4650-9a12-2541e4ae0c76,
  abstract     = {Congenital thrombotic thrombocytopenic purpura (TTP) is associated with ADAMTS13 mutations. The major site of ADAMTS13 synthesis is the liver. Expression in other tissues, and in TTP, has not been shown. In this study, ADAMTS13 protein expression was investigated in normal kidney and in renal tissue from two TTP patients, with a compound heterozygous mutation (P353L and P457L) and a homozygous mutation (4143insA). Real-time polymerase chain reaction demonstrated ADAMTS13 mRNA in normal kidney. ADAMTS13 was detected in the glomeruli and tubuli of normal and TTP kidney using anti-ADAMTS13 antibodies. In the glomeruli, expression was localised to podocytes (as demonstrated by counterstaining with two podocyte markers) and endothelium. Similar distribution was detected in the TTP kidneys. Electron microscopy detected ADAMTS13 in podocytes, endothelium and glomerular basement membrane. Cultured human podocytes expressed ADAMTS13 mRNA and protein, and podocyte lysate exhibited von Willebrand factor-cleaving activity. Mutation expression studies of the P353L and P457L mutations showed partially impaired secretion and lower activity of the secreted mutants. Impaired secretion has previously been shown for the 4143insA mutation. Podocyte-derived ADAMTS13 may offer local protection in the high-shear microcirculation of the glomerulus. The mutations in the two TTP patients studied enabled protein expression in the podocytes but affected protease secretion.},
  author       = {Manea Hedström, Minola and Kristoffersson, Ann-Charlotte and Schneppenheim, Reinhard and Saleem, Moin A. and Mathieson, Peter W. and Mörgelin, Matthias and Björk, Peter and Holmberg, Lars and Karpman, Diana},
  issn         = {0007-1048},
  keyword      = {thrombotic thrombocytopenic purpura,endothelial cells,podocytes,kidney,ADAMTS13},
  language     = {eng},
  number       = {5},
  pages        = {651--662},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {British Journal of Haematology},
  title        = {Podocytes express ADAMTS13 in normal renal cortex and in patients with thrombotic thrombocytopenic purpura},
  url          = {http://dx.doi.org/10.1111/j.1365-2141.2007.06694.x},
  volume       = {138},
  year         = {2007},
}