School of Medicine, Nantong University, Nantong, 226001, Jiangsu, China.
Nantong University, Nantong, Jiangsu, China.
Biochem Biophys Res Commun. 2018 Sep 3;503(1):202-208. doi: 10.1016/j.bbrc.2018.06.003. Epub 2018 Jun 6.
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.
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。