Functional regulation of von Willebrand factor ameliorates acute ischemia-reperfusion kidney injury in mice. 2019

Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
Departments of General Medicine, Nara Medical University, Kashihara, Japan.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D003404 Creatinine Creatinine Sulfate Salt,Krebiozen,Salt, Creatinine Sulfate,Sulfate Salt, Creatinine
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071120 ADAMTS13 Protein An ADAMTS protease that contains eight thrombospondin (TS) motifs. It cleaves VON WILLEBRAND FACTOR to control vWF-mediated THROMBOSIS. Mutations in the ADAMTS13 gene have been identified in familial cases of PURPURA, THROMBOTIC THROMBOCYTOPENIC and defects in ADAMTS13 activity are associated with MYOCARDIAL INFARCTION; BRAIN ISCHEMIA; PRE-ECLAMPSIA; and MALARIA. A Disintegrin and Metalloproteinase with Thrombospondin Motifs 13 Protein,ADAMTS-13 Protein,ADAMTS13 Protease,vWF-Cleaving Protease,von Willebrand Factor-Cleaving Protease,ADAMTS 13 Protein,vWF Cleaving Protease,von Willebrand Factor Cleaving Protease
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014841 von Willebrand Factor A high-molecular-weight plasma protein, produced by endothelial cells and megakaryocytes, that is part of the factor VIII/von Willebrand factor complex. The von Willebrand factor has receptors for collagen, platelets, and ristocetin activity as well as the immunologically distinct antigenic determinants. It functions in adhesion of platelets to collagen and hemostatic plug formation. The prolonged bleeding time in VON WILLEBRAND DISEASES is due to the deficiency of this factor. Factor VIII-Related Antigen,Factor VIIIR-Ag,Factor VIIIR-RCo,Plasma Factor VIII Complex,Ristocetin Cofactor,Ristocetin-Willebrand Factor,von Willebrand Protein,Factor VIII Related Antigen,Factor VIIIR Ag,Factor VIIIR RCo,Ristocetin Willebrand Factor
D015427 Reperfusion Injury Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA. Ischemia-Reperfusion Injury,Injury, Ischemia-Reperfusion,Injury, Reperfusion,Reperfusion Damage,Damage, Reperfusion,Injury, Ischemia Reperfusion,Ischemia Reperfusion Injury,Ischemia-Reperfusion Injuries,Reperfusion Damages,Reperfusion Injuries
D017353 Gene Deletion A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. Deletion, Gene,Deletions, Gene,Gene Deletions

Related Publications

Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
March 1993, Annals of the rheumatic diseases,
Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
December 2023, International journal of hematology,
Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
May 2020, International journal of molecular sciences,
Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
May 2018, Transplantation proceedings,
Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
December 2025, Renal failure,
Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
June 2014, Pharmacology research & perspectives,
Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
November 2017, Nephrology (Carlton, Vic.),
Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
June 2025, Hepatology research : the official journal of the Japan Society of Hepatology,
Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
February 2009, Laboratory investigation; a journal of technical methods and pathology,
Shiro Ono, and Hideto Matsui, and Masashi Noda, and Shogo Kasuda, and Noritaka Yada, and Kiyomi Yoshimoto, and Masashi Akiyama, and Toshiyuki Miyata, and Mitsuhiko Sugimoto, and Kenji Nishio
February 2023, The Journal of surgical research,
Copied contents to your clipboard!