Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Aim: Hepatorenal syndrome-induced acute kidney injury (AKI) comprises AKI and liver cirrhosis (LC) and is a risk factor for poor prognoses of patients with LC. Decreased a disintegrin-like metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) activity and increased von Willebrand factor (vWF) antigen levels are associated with LC progression and portal hypertension. We investigated the role of the ADAMTS13-vWF axis in AKI using an LC mouse model.
Methods: Wild-type and ADAMTS13-deficient (Adamts13) 129+Ter/Sv mice comprised the negative control and AKI groups. AKI was induced by intraperitoneal carbon tetrachloride, a single injection of a double dose of carbon tetrachloride, and lipopolysaccharide administration. Wild-type and vWF-deficient C57/B6J mice comprised a secondary animal model. Effects of ADAMTS13 alterations on liver and kidney injuries, and the role of vWF in AKI in the cirrhotic mouse model were analyzed.
Results: AKI groups of wild-type and Adamts13 mice showed increased serum aspartate aminotransferase/alanine aminotransferase and blood urea nitrogen/creatinine levels. Significantly greater changes in Adamts13 mice were observed. Blood flow in the liver and kidney was significantly decreased in the AKI group of Adamts13 mice. The AKI group of Adamts13 mice also demonstrated inflammatory changes, including increased F4/80-positive cells and renal injury markers in the kidney. Oxidative stress markers were increased in Adamts13 mice after AKI induction. Conversely, vWF-deficient mice were protected from liver and kidney damage, and showed reduced tissue blood flow, inflammation, and oxidative stress responses.
Conclusion: An imbalanced ADAMTS13-vWF axis may play a critical role in AKI progression with LC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/hepr.14181 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Thrombotic Thrombocytopenic Purpura (TTP) is caused by congenital or acquired deficiency of ADAMTS13, a metalloproteinase that cleaves von Willebrand Factor (vWF) multimers. Current treatments-plasma exchange and immunosuppression-are costly and associated with significant morbidity therefore, alternative strategies are needed. We developed the kitJak2 platform for producing genetically engineered lab-grown red blood cells (lgRBCs) as drug delivery vectors.
View Article and Find Full Text PDFRecombinant human ADAMTS13 attenuates LPS-induced acute kidney injury and renal microangiopathy in murine advanced liver fibrosis by cleaving vWF.
Biochim Biophys Acta Mol Cell Res
October 2025
Department of Gastroenterology, Nara Medical University, Kashihara, Nara, Japan.
Hepatorenal syndrome (HRS) has a poor prognosis among the complication of cirrhosis, yet treatment options are limited. Thrombotic microangiopathy with reduced ADAMTS13 activity and vWF accumulation has been reported to play a key role in the pathogenesis of acute kidney injury (AKI) in cirrhosis. This study investigated the effect of recombinant ADAMTS13 (rADAMTS13) on AKI with carbon tetrachloride (CCl)-induced advanced liver fibrosis in mice.
View Article and Find Full Text PDFADAMTS-13 Prevents VWF-Mediated Gastric Cancer Metastasis.
Arterioscler Thromb Vasc Biol
July 2025
Institute of Pathology, School of Basic Medical Sciences (C.-y.W., M.W., C.-y.Z., Q.Z., X.-y.Z., J.-m.D., C.-p.D., C.-l.Z., Y.D., A.-j.Y., M.L.), Lanzhou University, China.
Background: Gastric cancer invades local tissue extensively and metastasizes through the circulation to remote organs. Patients with metastasized gastric cancer have poor clinical outcomes. The vasculature in the cancer niche is developed poorly, thus allowing cancer cells to be released into the circulation.
View Article and Find Full Text PDFInvolvement of the ADAMTS13-von Willebrand factor axis in acute kidney injury in mice with liver cirrhosis.
Hepatol Res
June 2025
Department of Gastroenterology, Nara Medical University, Kashihara, Japan.
Aim: Hepatorenal syndrome-induced acute kidney injury (AKI) comprises AKI and liver cirrhosis (LC) and is a risk factor for poor prognoses of patients with LC. Decreased a disintegrin-like metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS13) activity and increased von Willebrand factor (vWF) antigen levels are associated with LC progression and portal hypertension. We investigated the role of the ADAMTS13-vWF axis in AKI using an LC mouse model.
View Article and Find Full Text PDFComparison of the Novel Thrombolytic Constitutively Active ADAMTS13 With Clinical Thrombolytics in a Murine Stroke Model.
Stroke
June 2025
Division of Neuroscience, School of Biological Sciences (L.R., G.C., K.S., S.M.A.), Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, United Kingdom.
Background: r-tPA (recombinant tissue-type plasminogen activator) and its variant, TNK (tenecteplase), are the currently approved thrombolytic drugs for the treatment of acute ischemic stroke, but they are ineffective in a proportion of patients due to r-tPA resistance of platelet-rich thrombi. A novel thrombolytic, caADAMTS13 (constitutively active a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) has been shown to improve experimental stroke outcomes where platelet-rich thrombi are present but have not been directly compared with r-tPA or TNK.
Methods: We conducted a direct comparison of caADAMTS13 versus r-tPA versus TNK versus vehicle control in the ferric chloride-mediated distal middle cerebral artery occlusion model in mice, which features platelet and VWF (von Willebrand Factor)-rich thrombi that reproduce r-tPA-resistant occlusion.