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

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Podocytes express ADAMTS13 in normal renal cortex and in patients with thrombotic thrombocytopenic purpura. / Manea Hedström, Minola; Kristoffersson, Ann-Charlotte; Schneppenheim, Reinhard; Saleem, Moin A.; Mathieson, Peter W.; Mörgelin, Matthias; Björk, Peter; Holmberg, Lars; Karpman, Diana.

I: British Journal of Haematology, Vol. 138, Nr. 5, 2007, s. 651-662.

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Manea Hedström, Minola ; Kristoffersson, Ann-Charlotte ; Schneppenheim, Reinhard ; Saleem, Moin A. ; Mathieson, Peter W. ; Mörgelin, Matthias ; Björk, Peter ; Holmberg, Lars ; Karpman, Diana. / Podocytes express ADAMTS13 in normal renal cortex and in patients with thrombotic thrombocytopenic purpura. I: British Journal of Haematology. 2007 ; Vol. 138, Nr. 5. s. 651-662.

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TY - JOUR

T1 - Podocytes express ADAMTS13 in normal renal cortex and in patients with thrombotic thrombocytopenic purpura

AU - Manea Hedström, Minola

AU - Kristoffersson, Ann-Charlotte

AU - Schneppenheim, Reinhard

AU - Saleem, Moin A.

AU - Mathieson, Peter W.

AU - Mörgelin, Matthias

AU - Björk, Peter

AU - Holmberg, Lars

AU - Karpman, Diana

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Paediatrics (Lund) (013002000), Emergency medicine/Medicine/Surgery (013240200), Division of Infection Medicine (BMC) (013024020)

PY - 2007

Y1 - 2007

N2 - 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.

AB - 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.

KW - thrombotic thrombocytopenic purpura

KW - endothelial cells

KW - podocytes

KW - kidney

KW - ADAMTS13

U2 - 10.1111/j.1365-2141.2007.06694.x

DO - 10.1111/j.1365-2141.2007.06694.x

M3 - Article

VL - 138

SP - 651

EP - 662

JO - British Journal of Haematology

T2 - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 5

ER -