Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis.
Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis.
复制标题
DOI：
10.1006/mthe.2002.0590
复制
发表时间：
2002-05
期刊：
影响因子：
--
通讯作者：
G. Yin;Weiming Liu;P. An;Ping Li;I. Ding;V. Planelles;E. Schwarz;W. Min
中科院分区：
文献类型：
--
作者：
G. Yin;Weiming Liu;P. An;Ping Li;I. Ding;V. Planelles;E. Schwarz;W. Min
类风湿性关节炎是炎性血管生成疾病的常见例子，其由促炎性和促血管生成细胞因子例如肿瘤坏死因子(TNF)介导。为了评估强效抗血管生成因子内皮抑素对 TNF 诱导的炎症性关节炎的作用，我们在疾病发作前将表达内皮抑素的慢病毒载体直接注射到人 TNF 转基因小鼠的关节中。 8周后对注射关节的组织学分析表明，内皮抑素降低了滑膜组织内的血管密度和总体平均关节炎指数。对内皮抑素抑制关节炎的潜在机制进行的体外和体内检查表明，内皮抑素可阻断 TNF 诱导的 JNK 激活和 JNK 依赖性促血管生成基因表达。这些数据表明内皮抑素抑制血管生成的新机制，并证明了抗血管生成基因疗法在治疗炎症性关节炎方面的潜在用途。
Rheumatoid arthritis is a prevalent example of an inflammatory angiogenic disease, which is mediated by pro-inflammatory and pro-angiogenic cytokines such as tumor necrosis factor (TNF). To evaluate the effect of the potent anti-angiogenic factor endostatin on TNF-induced inflammatory arthritis, we injected an endostatin-expressing lentiviral vector directly into the joints of human TNF-transgenic mice before the onset of disease. Histological analysis of the injected joints 8 weeks later revealed that endostatin reduced blood vessel density within the synovial tissues and an overall mean arthritis index. In vitro and in vivo examination of the potential mechanism by which endostatin inhibited the arthritis revealed that endostatin blocks TNF-induced activation of JNK and JNK-dependent pro-angiogenic gene expression. These data suggest a novel mechanism by which endostatin inhibits angiogenesis, and demonstrates the potential utility of anti-angiogenic gene therapy for treatment of inflammatory arthritis.