机构:[1]Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.[2]Department of Ophthalmology, The Third People’s Hospital of Dalian, Dalian Medical University, Dalian 116033, China.[3]Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology & Visual Science Key Lab, Beijing 100730, China.首都医科大学附属北京同仁医院首都医科大学附属同仁医院[4]Birth Defects Center, University of Louisville School of Dentistry, Louisville, KY 40202, USA.[5]James Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Angiogenesis is required for tissue repair; but abnormal angiogenesis or neovascularization (NV) causes diseases in the eye. The avascular status in the cornea is a prerequisite for corneal clarity and thought to be maintained by the equilibrium between proangiogenic and antiangiogenic factors that controls proliferation and migration of vascular endothelial cells (ECs) sprouting from the pericorneal plexus. VEGF is the most important intrinsic factor for angiogenesis; anti-VEGF therapies are available for treating ocular NV. However, the effectiveness of the therapies is limited because of VEGF-independent mechanism(s). We show that Zeb1 is an important factor promoting vascular EC proliferation and corneal NV; and a couple of small molecule inhibitors can evict Ctbp from the Zeb1-Ctbp complex, thereby reducing EC Zeb1 expression, proliferation, and corneal NV. We conclude that Zeb1-regulation of angiogenesis is independent of Vegf and that the ZEB1-CtBP inhibitors can be of potential therapeutic significance in treating corneal NV. Jin et al. demonstrate the importance of ZEB1 in the formation of corneal neovascularization in a VEGF-independent manner using in vitro and in vivo models. They further show that small molecule inhibitors can evict Ctbp from the Zeb1-Ctbp complex, thereby reducing endothelial cell Zeb1 expression, proliferation, and corneal neovascularization.
基金:
Natural Science Foundation of Liaoling Province [2019-MS-068, 201602210, 20180550976]; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [EY024110, P20GM103453]; Basic Research Grant of University of Louisville School of Medicine [E0819]; Research to Prevent BlindnessResearch to Prevent Blindness (RPB)
第一作者机构:[1]Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.[2]Department of Ophthalmology, The Third People’s Hospital of Dalian, Dalian Medical University, Dalian 116033, China.
共同第一作者:
通讯作者:
通讯机构:[1]Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, Louisville, KY 40202, USA.[4]Birth Defects Center, University of Louisville School of Dentistry, Louisville, KY 40202, USA.[5]James Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202, USA.
推荐引用方式(GB/T 7714):
Jin Lei,Zhang Yingnan,Liang Wei,et al.Zeb1 promotes corneal neovascularization by regulation of vascular endothelial cell proliferation[J].COMMUNICATIONS BIOLOGY.2020,3(1):doi:10.1038/s42003-020-1069-z.
APA:
Jin, Lei,Zhang, Yingnan,Liang, Wei,Lu, Xiaoqin,Piri, Niloofar...&Liu, Yongqing.(2020).Zeb1 promotes corneal neovascularization by regulation of vascular endothelial cell proliferation.COMMUNICATIONS BIOLOGY,3,(1)
MLA:
Jin, Lei,et al."Zeb1 promotes corneal neovascularization by regulation of vascular endothelial cell proliferation".COMMUNICATIONS BIOLOGY 3..1(2020)