EFEMP1 Overexpression Contributes to Neovascularization in Age-Related Macular Degeneration.
EFEMP1 Overexpression Contributes to Neovascularization in Age-Related Macular Degeneration.
复制标题
EFEMP1 过度表达有助于年龄相关性黄斑变性的新生血管形成
DOI：
10.3389/fphar.2020.547436
复制
发表时间：
2020
影响因子：
5.6
通讯作者：
Xu X
中科院分区：
文献类型：
--
作者：
Cheng L;Chen C;Guo W;Liu K;Zhao Q;Lu P;Yu F;Xu X
目的：视网膜相关性黄斑变性（AMD）是导致失明的主要原因之一，并且AMD中的脉络膜新生血管（CNV）可导致严重的视力损害。人类眼组织的基因表达谱具有揭示AMD的病理生理学的巨大潜力。本研究旨在鉴定AMD的新分子生物标志物和基因表达特征。研究方法：我们使用公开可用的数据集（GSE 29801）分析了来自AMD供体患者的视网膜脉络膜组织中的转录组谱，并与来自健康对照的那些进行了比较。我们集中在EFEMP 1基因，这是发现差异上调AMD，特别是在湿性AMD的眼睛。采用酶联免疫吸附试验（ELISA）进行血清学验证分析，以验证EFEMP 1在39例湿性AMD患者和39例年龄和性别匹配的白内障对照中的表达。然后，我们通过体外实验研究了EFEMP 1在血管生成中的作用，包括EFEMP 1在人脐静脉内皮细胞（HUVECs）中的过表达（OE）和敲低。结果如下：EFEMP 1在AMD患者的视网膜脉络膜组织中表达增加，湿性AMD比干性AMD更明显。此外，与对照组相比，湿性AMD患者血清中的fibulin-3（EFEMP 1编码蛋白）浓度显著升高。与对照组相比，EFEMP 1基因敲除的HUVECs小管形成和增殖能力明显降低，而EFEMP 1基因敲除的HUVECs小管形成和增殖能力明显增强。额外的细胞外纤蛋白-3处理没有增加野生型和EFEMP 1敲低的HUVEC的管形成和增殖，表明EFEMP 1的促血管生成特性是细胞来源的。我们还发现，血管内皮细胞中的血管内皮生长因子的表达上调EFEMP 1过表达和下调EFEMP 1敲低。结论：我们的研究结果表明EFEMP 1是AMD中CNV的一种新的生物标志物，为开发湿性AMD药物和诊断提供了新的靶点。
Purpose: Age-related macular degeneration (AMD) is one of the leading causes of blindness, and choroidal neovascularization (CNV) in AMD can lead to serious visual impairment. Gene expression profiling of human ocular tissues have a great potential to reveal the pathophysiology of AMD. This study aimed to identify novel molecular biomarkers and gene expression signatures of AMD. Methods: We analyzed transcriptome profiles in retinal-choroid tissues derived from donor patients with AMD in comparison with those from healthy controls using a publicly available dataset (GSE29801). We focused on the EFEMP1 gene, which was found to be differentially upregulated in AMD, especially in wet AMD eyes. Serological validation analysis was carried out to verify the expression of EFEMP1 in 39 wet AMD patients and 39 age- and gender-matched cataract controls, using an enzyme-linked immunosorbent assay (ELISA). We then investigated the role of EFEMP1 in angiogenesis through in vitro experiments involving EFEMP1 overexpression (OE) and knockdown in human umbilical vein endothelial cells (HUVECs). Results: An increase in EFEMP1 expression was observed in the retinal-choroid tissues of eyes with AMD, which was more significant in wet AMD than in dry AMD. In addition, there was a significant increase in serum fibulin-3 (EFEMP1 encoded protein) concentration in patients with wet AMD compared with that in the controls. Tube formation and proliferation of EFEMP1-OE HUVECs increased significantly, whereas those of EFEMP1 knockdown HUVECs decreased significantly compared with those of the control. Additional extracellular fibulin-3 treatments did not increase tube formation and proliferation of wildtype and EFEMP1 knockdown HUVECs, indicating that the proangiogenic properties of EFEMP1 are of cell origin. We also found that vascular endothelial growth factor expression in HUVECs was upregulated by EFEMP1 overexpression and downregulated by EFEMP1 knockdown. Conclusion: Our findings demonstrate EFEMP1 as a novel biomarker for CNV in AMD, providing a new target for the development of wet AMD-directed pharmaceuticals and diagnostics.
登录
查看更多内容
影响因子：
4.4
作者：
Stanton JB;Marmorstein AD;Zhang Y;Marmorstein LY
通讯作者：
Marmorstein LY
影响因子：
11.2
作者：
Nandhu MS;Hu B;Cole SE;Erdreich-Epstein A;Rodriguez-Gil DJ;Viapiano MS
通讯作者：
Viapiano MS
DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
4.4
作者：
Roybal, CN;Marmorstein, LY;Abcouwer, SF
通讯作者：
Abcouwer, SF
影响因子：
11.2
作者：
Albig, AR;Neil, JR;Schiemann, WP
通讯作者：
Schiemann, WP