Biologically active ADAMTS13 is expressed in renal tubular epithelial cells

Manea, Minola; Tati, Ramesh; Karlsson, J.‐A.; Békássy, Zivile; Karpman, Diana

doi:10.1007/s00467-009-1262-2

Cited by 31 publications

(28 citation statements)

References 32 publications

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“…(39, 40) More recently, Manea et al proposed that ADAMTS13 expressed in tubular cells and podocytes may have other functions such as tissue remodeling in addition to simply cleaving VWF. (19, 41) Our results demonstrate the progressive reduction of placental ADAMTS13 levels from first to third trimester, suggesting the participation of ADAMTS13 proteolysis in human embryo implantation.…”

Section: Discussionmentioning

confidence: 53%

Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development

Feng

et al. 2017

ATVB

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Objective ADAMTS13 is primarily synthesized in liver. The biosynthesis and its physiological role in placenta are not known. Approach and Results We employed real time polymerase chain reaction (PCR), immunohistochemistry, and Western blotting analyses, as well as proteolytic cleavage of FRETS-VWF73 to determine ADAMTS13 expression in placenta and trophoblasts obtained from individuals with normal pregnancy and patients with severe preeclampsia. We also determined the role of ADAMTS13 in extravillous trophoblasts using a 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay, wound scratch assay, transwell migration assay, tube formation assay, and tissue outgrowth assays. We demonstrated that full-length and proteolytically active ADAMTS13 was expressed in normal human placenta, primarily in the trophoblasts and villous core fetal vessel endothelium during pregnancy. Placental expression of ADAMTS13 mRNA, protein, and proteolytic activity was at the highest levels during the first trimester and significantly reduced at the term of gestation. Additionally, significantly reduced levels of placental ADAMTS13 expression was detected under hypoxic conditions and in patients with preeclampsia. In addition, recombinant ADAMTS13 protease stimulated proliferation, migration, invasion, and network formation of trophoblastic cells in culture. Finally, knockdown of ADAMTS13 expression attenuated the ability of tube formation in HTR-8/SVNEO cells and the extravillous trophoblast outgrowth in placental explants. Conclusions Our results demonstrate for the first time the expression of ADAMTS13 mRNA and protein in normal and abnormal placental tissues and its role in promoting angiogenesis and trophoblastic cell development. The findings support the potential role of the ADAMTS13-von Willebrand factor pathway in normal pregnancy and pathogenesis of preeclampsia.

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Section: Discussionmentioning

confidence: 53%

Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development

Feng

et al. 2017

ATVB

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“…Microthrombi from D+HUS patients stain positive for fibrinogen and thrombin and have low levels of vWF. This is in contrast to thrombi of TTP patients, which exhibit predominantly vWF [56]. Shigatoxin, the virulence factor derived from enterohemorrhagic E. coli (EHEC) causes complex formation of platelets and leukocytes.…”

Section: Common Features and Novel Therapeutic Approachesmentioning

confidence: 92%

“…In addition, Shigatoxin induces C3 deposition on plateletmonocyte, and platelet-neutrophil complexes, which results in progression of complement activation leading further to C9 deposition and TCC formation. This type of platelet activation may contribute to the thrombotic event [56][57][58].…”

Section: Common Features and Novel Therapeutic Approachesmentioning

confidence: 99%

Novel developments in thrombotic microangiopathies: is there a common link between hemolytic uremic syndrome and thrombotic thrombocytic purpura?

Zipfel

Wolf²,

John

et al. 2011

Pediatr Nephrol

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Thrombotic microangiopathies (TMA) represent a spectrum of related disorders associated with newly formed thrombi that block perfusion and thus affect the function of either renal or neurological organs and tissue. Recent years have seen a dramatic development in the field of TMA and for the two major forms hemolytic uremic syndrome (HUS) and thrombocytopenic purpura (TTP), new genetic causes and also autoimmune forms have been identified. This development indicates a similar pathophysiology and suggests that the two acute disorders are based on common principles. HUS is primarily a kidney disease and TTP also develops in the kidney and at neurological sites. In HUS thrombi formation is likely due to a deregulated complement activation and inappropriate platelet activity. In TTP thrombi formation occurs because of inappropriate processing of released multimers of von Willebrand Factor (vWF). Defining both the similarities and the unique features of each disorder will open up new ways and concepts that are relevant for diagnosis, for therapy, and for the prognostic outcome of kidney transplantations. Here we summarize the most relevant topics and timely issues that were presented and discussed at the 4th International Workshop on Thrombotic Microangiopathies held in Weimar in October 2009 (www.hus-ttp.de).

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“…This shear stress corresponds to values in large veins and the descending aorta (27). In some experiments PGEC were first perfused with patient PPP combined with normal washed platelets followed by perfusion of normal plasma (as a source of ADAMTS13) or recombinant ADAMTS13 (rADAMTS13) (28) at a 1:25 dilution for an additional 5 min. To block the effect of ADAMTS13 (29) plasma/serum samples were pre-incubated with 20 mM ethylene diamine tetra-acetic acid (EDTA, Merck, Darmstadt, Germany) just before perfusion, in certain experiments.…”

Section: Methodsmentioning

confidence: 99%

Complement Activation Associated with ADAMTS13 Deficiency in Human and Murine Thrombotic Microangiopathy

Tati

Kristoffersson

Ståhl

et al. 2013

The Journal of Immunology

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This study addressed the contribution of ADAMTS13-deficiency to complement activation in thrombotic thrombocytopenic purpura (TTP). Renal tissue and blood samples were available from 12 TTP patients. C3 and C5b-9 deposition were demonstrated in the renal cortex of two TTP patients, by immunofluorescence and immunohistochemistry, respectively. C3 was also demonstrated in the glomeruli of Shiga toxin-2 treated Adamts13−/− mice (n=6 of 7) but less in mice that were not Shiga toxin-2-treated (n=1 of 8, p<0.05) or wild-type mice (n=0 of 7). TTP patient plasma (n=9) contained significantly higher levels of complement-coated endothelial microparticles than control plasma (n=13), as detected by flow cytometry. Exposure of histamine-stimulated primary glomerular endothelial cells to platelet-rich-plasma from patients, or patient platelet-poor-plasma combined with normal platelets, in a perfusion system, under shear, induced C3 deposition on von Willebrand factor (VWF)-platelet strings (on both VWF and platelets) and on endothelial cells. Complement activation occurred via the alternative pathway. No C3 was detected when cells were exposed to TTP plasma that was pre-incubated with EDTA or heat-inactivated, or to control plasma. In the perfusion system patient plasma induced more release of C3- and C9-coated endothelial microparticles compared to control plasma. The results indicate that the microvascular process induced by ADAMTS13 deficiency triggers complement activation on platelets and the endothelium, which may contribute to formation of thrombotic microangiopathy.

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Biologically active ADAMTS13 is expressed in renal tubular epithelial cells

Cited by 31 publications

References 32 publications

Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development

Expression of ADAMTS13 in Normal and Abnormal Placentae and Its Potential Role in Angiogenesis and Placenta Development

Novel developments in thrombotic microangiopathies: is there a common link between hemolytic uremic syndrome and thrombotic thrombocytic purpura?

Complement Activation Associated with ADAMTS13 Deficiency in Human and Murine Thrombotic Microangiopathy

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