Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice

Abstract Acute kidney injury (AKI), an abrupt loss of renal function, is often seen in clinical settings and may become fatal. In addition to its hemostatic functions, von Willebrand factor (VWF) is known to play a role in cross-talk between inflammation and thrombosis. We hypothesized that VWF may...

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Autores principales:	Shiro Ono, Hideto Matsui, Masashi Noda, Shogo Kasuda, Noritaka Yada, Kiyomi Yoshimoto, Masashi Akiyama, Toshiyuki Miyata, Mitsuhiko Sugimoto, Kenji Nishio
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/580ebd31650b431a94c0d6f312e0a87b
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spelling	oai:doaj.org-article:580ebd31650b431a94c0d6f312e0a87b2021-12-02T15:09:20ZFunctional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice10.1038/s41598-019-51013-22045-2322https://doaj.org/article/580ebd31650b431a94c0d6f312e0a87b2019-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-51013-2https://doaj.org/toc/2045-2322Abstract Acute kidney injury (AKI), an abrupt loss of renal function, is often seen in clinical settings and may become fatal. In addition to its hemostatic functions, von Willebrand factor (VWF) is known to play a role in cross-talk between inflammation and thrombosis. We hypothesized that VWF may be involved in the pathophysiology of AKI, major causes of which include insufficient renal circulation or inflammatory cell infiltration in the kidney. To test this hypothesis, we studied the role of VWF in AKI using a mouse model of acute ischemia-reperfusion (I/R) kidney injury. We analyzed renal function and blood flow in VWF-gene deleted (knock-out; KO) mice. The functional regulation of VWF by ADAMTS13 or a function-blocking anti-VWF antibody was also evaluated in this pathological condition. Greater renal blood flow and lower serum creatinine were observed after reperfusion in VWF-KO mice compared with wild-type (WT) mice. Histological analysis also revealed a significantly lower degree of tubular damage and neutrophil infiltration in kidney tissues of VWF-KO mice. Both human recombinant ADAMTS13 and a function-blocking anti-VWF antibody significantly improved renal blood flow, renal function and histological findings in WT mice. Our results indicate that VWF plays a role in the pathogenesis of AKI. Proper functional regulation of VWF may improve the microcirculation and vessel function in the kidney, suggesting a novel therapeutic option against AKI.Shiro OnoHideto MatsuiMasashi NodaShogo KasudaNoritaka YadaKiyomi YoshimotoMasashi AkiyamaToshiyuki MiyataMitsuhiko SugimotoKenji NishioNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-8 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shiro Ono Hideto Matsui Masashi Noda Shogo Kasuda Noritaka Yada Kiyomi Yoshimoto Masashi Akiyama Toshiyuki Miyata Mitsuhiko Sugimoto Kenji Nishio Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice
description	Abstract Acute kidney injury (AKI), an abrupt loss of renal function, is often seen in clinical settings and may become fatal. In addition to its hemostatic functions, von Willebrand factor (VWF) is known to play a role in cross-talk between inflammation and thrombosis. We hypothesized that VWF may be involved in the pathophysiology of AKI, major causes of which include insufficient renal circulation or inflammatory cell infiltration in the kidney. To test this hypothesis, we studied the role of VWF in AKI using a mouse model of acute ischemia-reperfusion (I/R) kidney injury. We analyzed renal function and blood flow in VWF-gene deleted (knock-out; KO) mice. The functional regulation of VWF by ADAMTS13 or a function-blocking anti-VWF antibody was also evaluated in this pathological condition. Greater renal blood flow and lower serum creatinine were observed after reperfusion in VWF-KO mice compared with wild-type (WT) mice. Histological analysis also revealed a significantly lower degree of tubular damage and neutrophil infiltration in kidney tissues of VWF-KO mice. Both human recombinant ADAMTS13 and a function-blocking anti-VWF antibody significantly improved renal blood flow, renal function and histological findings in WT mice. Our results indicate that VWF plays a role in the pathogenesis of AKI. Proper functional regulation of VWF may improve the microcirculation and vessel function in the kidney, suggesting a novel therapeutic option against AKI.
format	article
author	Shiro Ono Hideto Matsui Masashi Noda Shogo Kasuda Noritaka Yada Kiyomi Yoshimoto Masashi Akiyama Toshiyuki Miyata Mitsuhiko Sugimoto Kenji Nishio
author_facet	Shiro Ono Hideto Matsui Masashi Noda Shogo Kasuda Noritaka Yada Kiyomi Yoshimoto Masashi Akiyama Toshiyuki Miyata Mitsuhiko Sugimoto Kenji Nishio
author_sort	Shiro Ono
title	Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice
title_short	Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice
title_full	Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice
title_fullStr	Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice
title_full_unstemmed	Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice
title_sort	functional regulation of von willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/580ebd31650b431a94c0d6f312e0a87b
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Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice

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