TEM7 (PLXDC1) in neovascular endothelial cells of fibrovascular membranes from patients with proliferative diabetic retinopathy.
TEM7 (PLXDC1) in neovascular endothelial cells of fibrovascular membranes from patients with proliferative diabetic retinopathy.
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DOI：
10.1167/iovs.07-1249
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发表时间：
2008-07
影响因子：
4.4
通讯作者：
Y. Yamaji;S. Yoshida;K. Ishikawa;Akihito Sengoku;Kota Sato;A. Yoshida;R. Kuwahara;K. Ohuchida;E. Oki;H. Enaida;K. Fujisawa;T. Kono;T. Ishibashi
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文献类型：
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作者：
Y. Yamaji;S. Yoshida;K. Ishikawa;Akihito Sengoku;Kota Sato;A. Yoshida;R. Kuwahara;K. Ohuchida;E. Oki;H. Enaida;K. Fujisawa;T. Kono;T. Ishibashi
糖尿病视网膜病变（PDR）是由于眼底后部纤维血管膜（FVM）的形成而导致的严重视力下降。肿瘤内皮标志物7（TEM 7）是一种在肿瘤内皮细胞中高度表达的蛋白质，但它是否在FVM中发挥作用尚不清楚。本研究的目的是确定TEM 7是否与FVM的形成有关。方法对PDR患者行玻璃体切割术，获取FVM。进行RT-PCR以确定TEM 7的mRNA的表达水平。通过直接测序鉴定TEM 7的剪接变体。免疫组织化学分析和原位杂交进行，以确定在FVM的TEM 7的网站。结果TEM 7 mRNA在10例FVM中有10例高表达，而在5例特发性视网膜前膜中几乎检测不到。亚克隆的TEM 7 PCR产物的直接测序揭示了FVM中的几种剪接变体（TEM 7的细胞内、分泌和膜结合形式）。免疫组化分析显示，TEM 7和CD 34，内皮细胞标记物，在大多数新生血管内皮细胞的FVM的共定位。免疫电子显微镜显示，膜结合的TEM 7的血管内皮细胞的FVM的管腔表面上的表达。结论TEM 7可能在FVM新生血管内皮细胞的增殖和维持中起重要作用。如果正确的话，TEM 7可能成为PDR新诊断和治疗策略的分子靶点。
PURPOSE Proliferative diabetic retinopathy (PDR) results from the formation of fibrovascular membranes (FVMs) in the posterior fundus that can lead to a severe decrease of vision. Tumor endothelial marker 7 (TEM7) is a protein that is highly expressed in the endothelial cells of tumors, but whether it plays a role in FVMs is unknown. The purpose of this study was to determine whether TEM7 is associated with the formation of FVMs. METHODS FVMs were obtained during vitrectomy from patients with PDR. RT-PCR was performed to determine the level of expression of the mRNA of TEM7. The splice variants of TEM7 were identified by direct sequencing. Immunohistochemical analyses and in situ hybridization was performed to determine the sites of TEM7 in the FVMs. RESULTS The level of the mRNA of TEM7 was high in 10 of 10 FVMs but was barely detectable in the five idiopathic epiretinal membranes. Direct sequencing of subcloned TEM7 PCR products revealed several splice variants (intracellular, secreted, and membrane-bound forms of TEM7) in the FVMs. Immunohistochemical analysis showed a colocalization of TEM7 and CD34, an endothelial cell marker, in most of the neovascular endothelial cells in the FVMs. Immunoelectron microscopy revealed that membrane-bound TEM7 was expressed on the luminal surfaces of the vascular endothelial cells of FVMs. CONCLUSIONS This study indicates that TEM7 may play a significant role in the proliferation and maintenance of neovascular endothelial cells in the FVMs. If correct, TEM7 may be a molecular target for new diagnostic and therapeutic strategies for PDR.