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TBK1 的抑制作用可减少体内外脉络膜新生血管的形成。

Inhibition of TBK1 reduces choroidal neovascularization in vitro and in vivo.

机构信息

School of Medicine, Nantong University, Nantong, 226001, Jiangsu, China.

Nantong University, Nantong, Jiangsu, China.

出版信息

Biochem Biophys Res Commun. 2018 Sep 3;503(1):202-208. doi: 10.1016/j.bbrc.2018.06.003. Epub 2018 Jun 6.

Abstract

choroidal neovascularization (CNV), a characteristic of wet age-related macular degeneration (AMD), causes severe vision loss among elderly patients. TANK-binding kinase 1 (TBK1) is a ubiquitously expressed serine-threonine kinase and is found to induce endothelial cells proliferation, represent a novel mediator of tumor angiogenesis and exert pro-inflammatory effect. However, the role of TBK1 in choroidal neovascularization has not been investigated so far. In this study, we found that the expression of TBK1 and VEGF was up-regulated in RF/6 A cells chemical hypoxia model and laser-induced mouse CNV model. Silencing of TBK1 suppressed the proliferation and tube formation activity of RF/6 A cells. Intravitreal injection of anti-TBK1 monoclonal antibody ameliorates CNV formation. Taken together, these findings exhibit a proangiogenic role for TBK1 via upregulating the expression of VEGF, and may suggest that TBK1 inhibition offers a unique and alternative method for prevention and treatment of AMD.

摘要

脉络膜新生血管(CNV)是湿性年龄相关性黄斑变性(AMD)的特征,可导致老年患者视力严重丧失。TANK 结合激酶 1(TBK1)是一种广泛表达的丝氨酸/苏氨酸激酶,被发现可诱导内皮细胞增殖,是肿瘤血管生成的新介质,并发挥促炎作用。然而,TBK1 在脉络膜新生血管中的作用尚未得到研究。在这项研究中,我们发现 TBK1 和 VEGF 的表达在 RF/6A 细胞化学缺氧模型和激光诱导的小鼠 CNV 模型中上调。TBK1 的沉默抑制了 RF/6A 细胞的增殖和管形成活性。玻璃体内注射抗 TBK1 单克隆抗体可改善 CNV 形成。总之,这些发现表明 TBK1 通过上调 VEGF 的表达发挥促血管生成作用,这可能表明 TBK1 抑制为 AMD 的预防和治疗提供了一种独特的替代方法。

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