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学科主题临床医学
Knockout of alpha A-Crystallin Inhibits Ocular Neovascularization
Xu, Qiong1; Bai, Yujing1; Huang, Lvzhen1; Zhou, Peng2; Yu, Wenzhen1; Zhao, Mingwei1
关键词alpha A-crystallin human umbilical vein endothelial cell neovascularization oxygen-induced retinopathy choroidal neovascularization vascular endothelial growth factor
刊名INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
2015-02-01
DOI10.1167/iovs.14-14734
56期:2页:816-826
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Ophthalmology
研究领域[WOS]Ophthalmology
关键词[WOS]ENDOTHELIAL GROWTH-FACTOR ; MURINE CORNEAL NEOVASCULARIZATION ; OXYGEN-INDUCED RETINOPATHY ; ANTI-VEGF THERAPY ; B-CRYSTALLIN ; CHOROIDAL NEOVASCULARIZATION ; MACULAR DEGENERATION ; RETINAL NEOVASCULARIZATION ; SIGNALING PATHWAYS ; EYE DISEASE
英文摘要

PURPOSE. The present study aimed to investigate the effects of alpha A-crystallin on pathologic ocular neovascularization.

METHODS. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro study, and alpha A-crystallin-knockout (CRYAA[-/-]) mice were used for the in vivo study. alpha A-crystallin was knocked down in HUVECs by using a specific small interfering RNA (siRNA), and the effects of aA-crystallin knockdown on proliferation, migration, tube formation, and apoptosis were evaluated. Enzyme-linked immunosorbent assays were performed to investigate extracellular concentrations of vascular endothelial growth factor (VEGF). In vivo mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) were generated by using CRYAA(-/-) mice. The nonperfused area in the OIR model was measured in flat-mounted retinas, and angiogenesis resulting in CNV was evaluated in retinal sections. Western blot analysis was performed to investigate the phosphorylation status of vascular endothelial growth factor receptor 2 (VEGFR2, high affinity receptor for VEGF), AKT, PLC gamma 1, FAK, Src, p42/p44MAPK, p38MAPK, caspase-3, and caspase-9 in cultured HUVECs, as well as in the OIR and CNV models.

RESULTS. The CRYAA siRNA not only induced HUVEC apoptosis but also inhibited exogenous and endogenous VEGF-induced cell activities, including proliferation, migration, and tube formation. Pathologic neovascularization was attenuated in the CRYAA(-/-) murine OIR and CNV models. Both in vitro and in vivo, the inhibition of angiogenesis was mediated by the suppression of VEGF secretion and the inhibition of the VEGFR2 signaling pathway; VEGFR2, AKT, PLC gamma 1, FAK, Src, p42/p44MAPK, and p38 MAPK all showed reduced phosphorylation levels. In addition, CRYAA knockout led to increased levels of cleaved caspase-9 and caspase-3.

CONCLUSIONS. Knockout of alpha A-crystallin inhibited pathologic neovascularization through the VEGF and VEGFR2 signaling pathways both in vitro and in vivo. These results suggest that alpha A-crystallin could be a novel pharmaceutical target for the prevention of ocular neovascularization.

语种英语
WOS记录号WOS:000352137300015
引用统计
被引频次:6[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66953
专题北京大学第二临床医学院
北京大学第二临床医学院_眼科
作者单位1.Peking Univ, Peoples Hosp, Beijing Key Lab Diag & Treatment Retinal & Choroi, Key Lab Vis Loss & Restorat,Minist Educ,Dept Opht, Beijing 100044, Peoples R China
2.Pkwy Hlth Inc, Shanghai, Peoples R China
推荐引用方式
GB/T 7714
Xu, Qiong,Bai, Yujing,Huang, Lvzhen,et al. Knockout of alpha A-Crystallin Inhibits Ocular Neovascularization[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,2015,56(2):816-826.
APA Xu, Qiong,Bai, Yujing,Huang, Lvzhen,Zhou, Peng,Yu, Wenzhen,&Zhao, Mingwei.(2015).Knockout of alpha A-Crystallin Inhibits Ocular Neovascularization.INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,56(2),816-826.
MLA Xu, Qiong,et al."Knockout of alpha A-Crystallin Inhibits Ocular Neovascularization".INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 56.2(2015):816-826.
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