Anti-inflammatory protective effect of ADAMTS-13 in murine arthritis models.
Anti-inflammatory protective effect of ADAMTS-13 in murine arthritis models.
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DOI：
10.1111/jth.15828
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发表时间：
2022-10
影响因子：
10.4
通讯作者：
Wagner, Denisa D.
中科院分区：
文献类型：
--
作者：
Fukui, Shoichi;Gutch, Sarah;Fukui, Saeko;Chu, Long;Wagner, Denisa D.
关键词：
类风湿性关节炎（RA）患者经常发生血栓形成事件，伴有内皮功能障碍。血管性血友病因子（VWF）已被证明结合中性粒细胞胞外陷阱（NET）和NET是RA病因的一部分。本研究旨在阐明这种血栓前状态是否会加重关节炎的炎症。在这里，我们专注于参与的解聚素和金属蛋白酶与血栓形成蛋白1型基序，成员13（ADAMTS-13），酶裂解VWF和其对NET沉积和RA的发展的影响。我们评估了Adamts 13基因和重组人ADAMTS-13（rhADAMTS-13）对胶原诱导的关节炎（CIA）小鼠模型中关节炎的影响。我们还评估了滑膜组织中的VWF和NET。几只Adamts 13 −/−小鼠患上了关节炎，而Adamts 13 +/+同胞则没有。Adamts 13 −/−的滑膜组织显示NET蓄积。用耐受良好剂量的rhADAMT 13治疗DBA/1 J小鼠（一种关节炎易感品系）降低了关节炎发病率并减轻了关节炎的严重程度。用rhADAMT 13治疗的小鼠呈现出更少的血清白细胞介素6和更少的骨侵蚀，这通过显微计算机断层扫描来确定。当主动施用rhADAMTS-13时以及当在关节炎发展后施用时，均观察到对关节炎严重程度的影响。在这两种情况下，rhADAMTS-13减少VWF和NET沉积在增殖的滑膜组织通过免疫印迹评价。我们的结果证明了Adamts-13在小鼠关节炎中的抑制作用和rhADAMTS-13治疗的有效性。此外，这项研究表明，VWF在滑膜中的沉积和随后的致病性NET保留促进关节炎。用rhADAMTS-13治疗提供了一种靶向关节炎中的炎症和血栓前状态的潜在治疗方法。
Patients with rheumatoid arthritis (RA) have frequent thrombotic events with endothelial dysfunction. Von Willebrand factor (VWF) has been shown to bind neutrophil extracellular traps (NETs) and NETs are part of RA etiology. This study aims to elucidate whether this prothrombotic status exacerbates inflammation in arthritis. Here we focus on the involvement of A Disintegrin And Metalloprotease with ThromboSpondin type 1 motif, member 13 (ADAMTS-13), an enzyme cleaving VWF and its effect on NET deposition and RA development. We evaluated the influence of the Adamts13 gene and recombinant human ADAMTS-13 (rhADAMTS-13) on arthritis in the mouse models of collagen-induced arthritis (CIA). We also assessed VWF and NETs in synovial tissue. Several Adamts13−/− mice developed arthritis, while Adamts13+/+ siblings did not. Synovial tissue from Adamts13−/− showed accumulation of NETs. Treatment of DBA/1 J mice, an arthritis-susceptible strain, with well-tolerated doses of rhADAMT13 reduced arthritis incidence and alleviated the severity of arthritis. Mice treated with rhADAMT13 presented less serum interleukin 6 and less bone erosion determined by micro-computed tomography. The effects on arthritis severity were observed both when administering rhADAMTS-13 prophylactically and also when given after arthritis has developed. In both conditions, rhADAMTS-13 reduced VWF and NET deposition on proliferated synovial tissue evaluated by immunoblotting. Our results demonstrate the inhibitory role of Adamts13 in murine arthritis and the effectiveness of rhADAMTS-13 treatment. Additionally, this study suggests that deposition of VWF in the synovium and subsequent pathogenic NET retention promotes arthritis. Treatment with rhADAMTS-13 provides a potential therapeutic approach targeting inflammation and pro-thrombotic state in arthritis.
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影响因子：
20.3
作者：
Pendu, Ronan;Terraube, Virginie;Denis, Cecile V.
通讯作者：
Denis, Cecile V.
影响因子：
8.8
作者：
Wong, Siu Ling;Goverman, Jeremy;Wagner, Denisa D.
通讯作者：
Wagner, Denisa D.
DOI：
10.1111/j.1538-7836.2012.04822.x
发表时间：
2012-08
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Khan MM;Motto DG;Lentz SR;Chauhan AK
通讯作者：
Chauhan AK
ADAMTS13：血栓形成与炎症之间的新联系。
影响因子：
15.3
作者：
Chauhan, Anil K.;Kisucka, Janka;Brill, Alexander;Walsh, Meghan T.;Scheiflinger, Friedrich;Wagner, Denisa D.
通讯作者：
Wagner, Denisa D.
影响因子：
17.1
作者：
Khandpur R;Carmona-Rivera C;Vivekanandan-Giri A;Gizinski A;Yalavarthi S;Knight JS;Friday S;Li S;Patel RM;Subramanian V;Thompson P;Chen P;Fox DA;Pennathur S;Kaplan MJ
通讯作者：
Kaplan MJ