TGF-β participates choroid neovascularization through Smad2/3-VEGF/TNF-α signaling in mice with Laser-induced wet age-related macular degeneration.
TGF-β participates choroid neovascularization through Smad2/3-VEGF/TNF-α signaling in mice with Laser-induced wet age-related macular degeneration.
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TGF-β通过激光诱导的与湿年龄相关的黄斑变性的小鼠中的SMAD2/3-VEGF/TNF-α信号参与脉络膜新血管化。
DOI：
10.1038/s41598-017-10124-4
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发表时间：
2017-08-29
影响因子：
4.6
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Wang X;Ma W;Han S;Meng Z;Zhao L;Yin Y;Wang Y;Li J
脉络膜新生血管（CNV）是年龄相关性黄斑变性（AMD）最严重的并发症，也是发达国家老年人不可逆失明的最常见原因。本研究旨在探讨转化生长因子-β(TGF-β)和Smad2/3-VEGF/TNF-α信号通路对CNV血管生成的影响，并在CNV小鼠模型中探讨TGF-β抑制剂对CNV发生的影响。眼底荧光素血管造影（FFA）评价激光诱导CNV的形成。用苏木精-伊红（HE）染色获得CNV病变组织学。免疫荧光染色检测TGF-β蛋白表达。Western blot检测TGF-β、磷酸化Smad2/3、VEGF、TNF-α的表达。用荧光素染色法在RPE/脉络膜-巩膜平片上分析CNV区。我们发现TGF-β蛋白的表达水平在CNV发育的第3周逐渐达到峰值。合成TGF-β抑制剂LY2157299或天然TGF-β抑制剂Decorin均可抑制CNV小鼠的VEGF和TNF-α蛋白水平显著升高。磷酸化的Smad2/3水平在CNV小鼠中显著升高，但这种反应被TGF-β抑制剂严重抑制。本研究表明TGF-β/Smad信号通过下调VEGF和TNF-α表达在激光诱导的CNV形成中发挥重要作用，提示TGF-β抑制剂可能为湿性AMD治疗提供传统方法的替代方法。
Choroidal neovascularization(CNV) is the most severe complication in Age-related macular degeneration(AMD) and the most common cause of irreversible blindness in the elderly in developed world. The aim of this study was to identify the effect of transforming growth factor-β(TGF-β) and Smad2/3-VEGF/TNF-α signaling on CNV angiopoiesis, and to explore TGF-β inhibitors on the development of CNV in a CNV mouse model. Fundus fluorescein angiography(FFA) was used to evaluate the laser-induced CNV formation. The histology of CNV lesions stained with hematoxylin-eosin(HE) was obtained. The immunofluorescent staining was performed to determine TGF-β protein expression. The expressions of TGF-β, phosphorylated Smad2/3, VEGF and TNF-α were determined by using Western blot analysis. The CNV areas were analyzed by using fluorescein stain on RPE/choroid-sclera flat mounts. We found the levels of TGF-β protein expression increasingly reached the peak till 3rd week during the CNV development. The protein levels of VEGF and TNF-α also increased significantly in CNV mice, which were inhibited by a synthetic TGF-β inhibitor LY2157299 or a natural TGF-β inhibitor Decorin. The phosphorylated Smad2/3 levels increased significantly in CNV mice, but this response was profoundly suppressed by the TGF-β inhibitors. Here we have demonstrated that TGF-β/Smad signaling plays an important role in Laser-induced CNV formation through down-regulation of VEGF and TNF-α expressions, suggesting TGF-β inhibitors may provide an alternative to traditional methods in wet AMD treatment.
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影响因子：
6
作者：
Lyzogubov, Valeriy;Wu, Xiaobo;Bora, Nalini S.
通讯作者：
Bora, Nalini S.
影响因子：
7.4
作者：
Nagineni, Chandrasekharam N.;Raju, Raghavan;Detrick, Barbara
通讯作者：
Detrick, Barbara
影响因子：
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作者：
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影响因子：
3.7
作者：
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通讯作者：
Li Q
影响因子：
3.4
作者：
Bian, Zong-Mei;Elner, Susan G.;Elner, Victor M.
通讯作者：
Elner, Victor M.