A C-type lectin from Bothrops jararacussu venom reprograms endothelial cell biology

IF 9.2 1区 医学 Q1 PERIPHERAL VASCULAR DISEASE Angiogenesis Pub Date : 2024-06-15 DOI:10.1007/s10456-024-09931-x
Federico G. Baudou, Nancy L. Charó, Marco A. Scheidegger, Juan C. Stupirski, Juan M. Pérez Sáez, María F. Troncoso, Mora Massaro, Adolfo R. de Roodt, Mauricio C. De Marzi, Mirta Schattner, Gabriel A. Rabinovich
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Abstract

Snake venoms are intricate mixtures of enzymes and bioactive factors that induce a range of detrimental effects in afflicted hosts. Certain Viperids, including Bothrops jararacussu, harbor C-type lectins (CTLs) known for their modulation of a variety of host cellular responses. In this study, we isolated and purified BjcuL, a CTL from B. jararacussu venom and investigated its impact on endothelial cell behavior, contrasting it with human galectin-1 (Gal-1), a prototype member of the galectin family with shared β-galactoside-binding activity. We found that BjcuL binds to human dermal microvascular endothelial cells (HMECs) in a concentration- and carbohydrate-dependent fashion and reprograms the function of these cells, favoring a pro-inflammatory and pro-coagulant endothelial phenotype. In light of the quest for universal antagonists capable of mitigating the harmful consequences of snake venoms, BjcuL emerges as a promising target to be blocked in order to regulate pathological endothelial cell responses.

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一种来自两头乌鸦毒液的 C 型凝集素可重塑内皮细胞生物学。
蛇毒是酶和生物活性因子的复杂混合物,会对受害宿主产生一系列有害影响。某些蝰蛇(包括蝮蛇)体内含有C型凝集素(CTL),可调节宿主细胞的各种反应。在这项研究中,我们分离并纯化了贾拉acussu蝰蛇毒液中的一种CTL--BjcuL,研究了它对内皮细胞行为的影响,并将其与人类半凝集素-1(Gal-1)进行了对比,后者是半凝集素家族的原型成员,具有共同的β-半乳糖苷结合活性。我们发现,BjcuL 能以浓度和碳水化合物依赖的方式与人真皮微血管内皮细胞(HMECs)结合,并对这些细胞的功能进行重编程,有利于形成促炎症和促凝血的内皮表型。鉴于人们正在寻找能够减轻蛇毒有害后果的通用拮抗剂,BjcuL 成为了一个有希望被阻断的靶点,以调节病理内皮细胞反应。
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来源期刊
Angiogenesis
Angiogenesis PERIPHERAL VASCULAR DISEASE-
CiteScore
21.90
自引率
8.20%
发文量
37
审稿时长
6-12 weeks
期刊介绍: Angiogenesis, a renowned international journal, seeks to publish high-quality original articles and reviews on the cellular and molecular mechanisms governing angiogenesis in both normal and pathological conditions. By serving as a primary platform for swift communication within the field of angiogenesis research, this multidisciplinary journal showcases pioneering experimental studies utilizing molecular techniques, in vitro methods, animal models, and clinical investigations into angiogenic diseases. Furthermore, Angiogenesis sheds light on cutting-edge therapeutic strategies for promoting or inhibiting angiogenesis, while also highlighting fresh markers and techniques for disease diagnosis and prognosis.
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