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Cited 2 time in webofscience Cited 2 time in scopus
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ADAMTS13-von Willebrand factor axis is involved in the pathophysiology of kidney ischaemia-reperfusion injury

Authors
Kim, Myung-GyuLim, Sung YoonKo, Yoon SookLee, Hee YoungJo, Sang-KyungCho, Won Yong
Issue Date
Nov-2017
Publisher
WILEY
Keywords
acute kidney injury; ADAMTS13; inflammation; thrombosis; von Willebrand factor
Citation
NEPHROLOGY, v.22, no.11, pp.913 - 920
Indexed
SCIE
SCOPUS
Journal Title
NEPHROLOGY
Volume
22
Number
11
Start Page
913
End Page
920
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/4454
DOI
10.1111/nep.12893
ISSN
1320-5358
Abstract
AimThe ADAMTS13-von Willebrand factor (vWF) axis has been suggested to play a critical role in the pathophysiology of ischaemia-reperfusion injury (IRI) in the heart or brain. Therefore, we aimed to investigate whether this axis was involved in the pathophysiology of IRI-induced acute kidney injury. MethodsWe performed renal IRI in ADAMTS13 knockout (KO) or wild type (WT) mice. Functional and histological kidney damage, and inflammation were compared and the effect of anti-vWF antibodies in ADAMTS13 KO mice was assessed. ResultsFollowing IRI, the blood and kidney ADAMTS13 levels were significantly decreased. vWF expression was significantly upregulated in both the medulla and cortex of injured kidneys as shown by immunohistochemistry and western blot analyses. There was also an increased level of vWF dimers after IRI. In ADAMTS13 KO mice, kidney vWF levels were further increased and this was associated with greater endothelial and epithelial injury compared to WT mice, suggesting an important role of vWF in renal IRI. In addition, the number of Gr-1(+) neutrophils was significantly higher in the kidneys of ADAMTS13 KO mice compared to WT mice, whereas F4/80 macrophage numbers were unchanged. In ADAMTS13 KO mice, administration of anti-vWF antibodies after IRI partially reversed renal injury. ConclusionOur data show that the ADAMTS13-vWF axis is partially involved in the pathophysiology of kidney IRI, suggesting that regulating ADAMTS13- and vWF-dependent mechanisms could have therapeutic potential to limit renal IRI. Summary at a Glance This manuscript demonstrates a link between the ADAMTS13 metalloprotease (known to cleave vWF and be involved in clotting as well as inflammatory responses) and acute kidney injury. ADAMTS13 deficient mice were found to have higher levels of renal vWF, greater endothelial injury, inflammation and kidney dysfunction.
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Cho, Won Yong
Anam Hospital (Department of Nephrology and Hypertension, Anam Hospital)
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