ADAMTS13-von Willebrand factor axis is involved in the pathophysiology of kidney ischaemia-reperfusion injury

Myung-Gyu Kim, Sung Yoon Lim, Yoon Sook Ko, Hee Young Lee, Sang Kyung Jo, Won Yong Cho

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2 Citations (Scopus)

Abstract

Aim: The 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. Methods: We 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. Results: Following 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. Conclusion: Our 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.

Original languageEnglish
Pages (from-to)913-920
Number of pages8
JournalNephrology
Volume22
Issue number11
DOIs
Publication statusPublished - 2017 Nov 1

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Keywords

  • acute kidney injury
  • ADAMTS13
  • inflammation
  • thrombosis
  • von Willebrand factor

ASJC Scopus subject areas

  • Nephrology

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