TGF-beta participates choroid neovascularization through Smad2/3-VEGF/TNF-alpha signaling in mice with Laser-induced wet age-related macular degeneration
单位：[1]Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, PR China.临床科室眼科眼科首都医科大学附属北京友谊医院[2]Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, PR China.[3]Beijing Stomatological Hospital, Capital Medical University, Beijing, 100050, PR China.
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-beta(TGF-beta) and Smad2/3-VEGF/TNF-alpha signaling on CNV angiopoiesis, and to explore TGF-beta 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-beta protein expression. The expressions of TGF-beta, phosphorylated Smad2/3, VEGF and TNF-alpha 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-beta protein expression increasingly reached the peak till 3rd week during the CNV development. The protein levels of VEGF and TNF-alpha also increased significantly in CNV mice, which were inhibited by a synthetic TGF-beta inhibitor LY2157299 or a natural TGF-beta inhibitor Decorin. The phosphorylated Smad2/3 levels increased significantly in CNV mice, but this response was profoundly suppressed by the TGF-beta inhibitors. Here we have demonstrated that TGF-beta/Smad signaling plays an important role in Laser-induced CNV formation through down-regulation of VEGF and TNF-alpha expressions, suggesting TGF-beta inhibitors may provide an alternative to traditional methods in wet AMD treatment.
基金：
Seed Grant of International Alliance of Translational Neuroscience [PXM2014-014226-000006]; Beijing Natural Science FoundationBeijing Natural Science Foundation [7141001]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [31171147, 31471142]; Beijing Ophthalmology & Visual Sciences Key Laboratory [2015YKSJ02]
第一作者单位：[1]Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, PR China.[2]Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, PR China.
共同第一作者：
通讯作者：
通讯机构：[1]Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, PR China.[2]Department of Neurobiology and Center of Stroke, Beijing Institute for Brain Disorders, Capital Medical University, Beijing, 100069, PR China.
推荐引用方式(GB/T 7714)：
Xiaolei Wang,Wei Ma,Song Han,et al.TGF-beta participates choroid neovascularization through Smad2/3-VEGF/TNF-alpha signaling in mice with Laser-induced wet age-related macular degeneration[J].SCIENTIFIC REPORTS.2017,7:doi:10.1038/s41598-017-10124-4.
APA：
Xiaolei Wang,Wei Ma,Song Han,Zhaoyang Meng,Lu Zhao...&Junfa Li.(2017).TGF-beta participates choroid neovascularization through Smad2/3-VEGF/TNF-alpha signaling in mice with Laser-induced wet age-related macular degeneration.SCIENTIFIC REPORTS,7,
MLA：
Xiaolei Wang,et al."TGF-beta participates choroid neovascularization through Smad2/3-VEGF/TNF-alpha signaling in mice with Laser-induced wet age-related macular degeneration".SCIENTIFIC REPORTS 7.(2017)
