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

Research output: Contribution to journalArticle

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

Fingerprint

von Willebrand Factor
Reperfusion Injury
Kidney
Knockout Mice
Kidney Cortex
Antibodies
Wounds and Injuries
Acute Kidney Injury
Neutrophils
Western Blotting
Immunohistochemistry
Macrophages
Inflammation
Brain

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

ADAMTS13-von Willebrand factor axis is involved in the pathophysiology of kidney ischaemia-reperfusion injury. / Kim, Myung-Gyu; Lim, Sung Yoon; Ko, Yoon Sook; Lee, Hee Young; Jo, Sang Kyung; Cho, Won Yong.

In: Nephrology, Vol. 22, No. 11, 01.11.2017, p. 913-920.

Research output: Contribution to journalArticle

@article{a8164aab30ab4086b02400b834471588,
title = "ADAMTS13-von Willebrand factor axis is involved in the pathophysiology of kidney ischaemia-reperfusion injury",
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.",
keywords = "acute kidney injury, ADAMTS13, inflammation, thrombosis, von Willebrand factor",
author = "Myung-Gyu Kim and Lim, {Sung Yoon} and Ko, {Yoon Sook} and Lee, {Hee Young} and Jo, {Sang Kyung} and Cho, {Won Yong}",
year = "2017",
month = "11",
day = "1",
doi = "10.1111/nep.12893",
language = "English",
volume = "22",
pages = "913--920",
journal = "Nephrology",
issn = "1320-5358",
publisher = "Wiley-Blackwell",
number = "11",

}

TY - JOUR

T1 - ADAMTS13-von Willebrand factor axis is involved in the pathophysiology of kidney ischaemia-reperfusion injury

AU - Kim, Myung-Gyu

AU - Lim, Sung Yoon

AU - Ko, Yoon Sook

AU - Lee, Hee Young

AU - Jo, Sang Kyung

AU - Cho, Won Yong

PY - 2017/11/1

Y1 - 2017/11/1

N2 - 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.

AB - 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.

KW - acute kidney injury

KW - ADAMTS13

KW - inflammation

KW - thrombosis

KW - von Willebrand factor

UR - http://www.scopus.com/inward/record.url?scp=85031496766&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031496766&partnerID=8YFLogxK

U2 - 10.1111/nep.12893

DO - 10.1111/nep.12893

M3 - Article

C2 - 27507004

AN - SCOPUS:85031496766

VL - 22

SP - 913

EP - 920

JO - Nephrology

JF - Nephrology

SN - 1320-5358

IS - 11

ER -