Inhibition of intracranial hemangioma growth and hemorrhage by TNFSF15
Inhibition of intracranial hemangioma growth and hemorrhage by TNFSF15
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TNFSF15抑制颅内血管瘤生长和出血
DOI：
10.1096/fj.201802758rrr
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发表时间：
2019-09-01
期刊：
影响因子：
4.8
通讯作者：
Li, Lu-Yuan
中科院分区：
文献类型：
--
作者：
Yang, Gui-Li;Han, Zhenying;Li, Lu-Yuan
血管母细胞瘤（HB）是一种异常的颅内血管积聚，表现出出血的巨大潜力。手术选择是有限的，并且很少有药物可用于治疗。我们在此通过免疫组织化学分析显示，与正常脑组织相比，HB病变显示VEGF表达水平和巨噬细胞/小胶质细胞浸润水平高度增加。同时，TNF超家族15 (TNFSF15)（也称为血管内皮生长抑制剂）是一种抗血管生成的细胞因子，在正常脑血管中高表达，但在HB病变中表达减少。我们用bEnd建立了小鼠脑血管瘤模型。产生大量VEGF的T抗原转化内皮细胞系的3个细胞。当植入小鼠大脑时，这些细胞形成的病变与HB的病理特征非常相似。逆转录病毒感染。3细胞携带TNFSF15可抑制VEGF的产生，延缓血管瘤的形成。野生型弯曲也得到了类似的结果。将3个细胞植入过表达TNFSF15的转基因小鼠脑内。此外，TNFSF15治疗可增强病变血管的周细胞覆盖，减少炎症细胞浸润，减少出血。这些发现表明，TNFSF15平衡HB微环境异常高的血管生成和炎症潜能的能力对治疗这种疾病具有治疗价值。杨,g . L。,汉族,Z,熊,J。,Wang年代,魏,H,秦,T . T。，肖辉，刘勇，徐丽霞。，祁建伟。，张志胜。蒋荣，张军，李丽英。TNFSF15对颅内血管瘤生长和出血的抑制作用。中国生物医学工程学报，2016,32(2):444 - 444。www.fasebj.org
Hemangioblastoma (HB) is an abnormal intracranial buildup of blood vessels that exhibit a great potential for hemorrhage. Surgical options are limited, and few medications are available for treatment. We show here by immunohistochemical analysis that HB lesions display highly increased levels of VEGF expression and macrophage/microglia infiltration compared with those in normal brain tissues. In the meantime, TNF superfamily 15 (TNFSF15) (also known as vascular endothelial growth inhibitor), an antiangiogenic cytokine, is highly expressed in normal brain blood vessels but diminished in HB lesions. We set up a brain hemangioma model by using mouse bEnd.3 cells of a T antigen—transformed endothelial cell line that produce a large amount of VEGF. When implanted in mouse brains, these cells form lesions that closely resemble the pathologic characteristics of HB. Retroviral infection of bEnd.3 cells with TNFSF15 leads to inhibition of VEGF production and retardation of hemangioma formation. Similar results are obtained when wild‐type bEnd.3 cells are implanted in the brains of transgenic mice overexpressing TNFSF15. Additionally, TNFSF15 treatment results in enhanced pericyte coverage of the blood vessels in the lesions together with reduced inflammatory cell infiltration and decreased hemorrhage. These findings indicate that the ability of TNFSF15 to counterbalance the abnormally highly angiogenic and inflammatory potential of the microenvironment of HB is of therapeutic value for the treatment of this disease.—Yang, G.‐L., Han, Z., Xiong, J., Wang, S., Wei, H., Qin, T.‐T., Xiao, H., Liu, Y., Xu, L.‐X., Qi, J.‐W., Zhang, Z.‐S., Jiang, R., Zhang, J., Li, L.‐Y. Inhibition of intracranial hemangioma growth and hemorrhage by TNFSF15. FASEB J. 33, 10505–10514 (2019). www.fasebj.org