Cargando…
Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation
PURPOSE: Age-related macular degeneration (AMD) is the leading cause of central visual loss among patients over the age of 55 years worldwide. Neovascular-type AMD (nAMD) accounts for approximately 10% of patients with AMD and is characterized by choroidal neovascularization (CNV). The proliferation...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Molecular Vision
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800432/ https://www.ncbi.nlm.nih.gov/pubmed/29422766 |
_version_ | 1783298204102557696 |
---|---|
author | Yan, Zhenzhen Shi, Haihong Zhu, Rongrong Li, Lele Qin, Bai Kang, Lihua Chen, Hui Guan, Huaijin |
author_facet | Yan, Zhenzhen Shi, Haihong Zhu, Rongrong Li, Lele Qin, Bai Kang, Lihua Chen, Hui Guan, Huaijin |
author_sort | Yan, Zhenzhen |
collection | PubMed |
description | PURPOSE: Age-related macular degeneration (AMD) is the leading cause of central visual loss among patients over the age of 55 years worldwide. Neovascular-type AMD (nAMD) accounts for approximately 10% of patients with AMD and is characterized by choroidal neovascularization (CNV). The proliferation of choroidal endothelial cells (CECs) is one important step in the formation of new vessels. Transcriptional coactivator Yes-associated protein (YAP) can promote the proliferation of multiple cancer cells, corneal endothelial cells, and vascular smooth muscle cells, which participate in angiogenesis. This study intends to reveal the expression and functions of YAP during the CNV process. METHODS: In the study, a mouse CNV model was generated by laser photocoagulation. YAP expression was detected with western blotting and immunohistochemistry. YAP siRNA and ranibizumab, a VEGF monoclonal antibody, were injected intravitreally in CNV mice. The YAP and VEGF expression levels after injection were detected with western blotting. The incidence and leakage area of CNV were measured with fundus fluorescein angiography, choroidal flat mounting, and hematoxylin and eosin (HE) staining. Immunofluorescent double staining was used to detect YAP cellular localization with CD31 (an endothelial cell marker) antibody. Proliferating cell nuclear antigen (PCNA) expression in CNV mice without or with YAP siRNA intravitreal injection and the colocalization of PCNA and CD31 were measured with western blotting and immunofluorescent double staining, respectively. RESULTS: YAP expression increased following laser exposure, in accordance with vascular endothelial growth factor (VEGF) expression. YAP siRNA and ranibizumab decreased VEGF expression and the incidence and leakage area of CNV. YAP was localized in the vascular endothelium within the CNV site. Additionally, after laser exposure, YAP siRNA inhibited the increased expression of PCNA, which was colocalized with endothelial cells. CONCLUSIONS: This study showed that YAP upregulation promoted CNV formation by upregulating the proliferation of endothelial cells, providing evidence for the molecular mechanisms of CNV and suggesting a novel molecular target for nAMD treatment. |
format | Online Article Text |
id | pubmed-5800432 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Molecular Vision |
record_format | MEDLINE/PubMed |
spelling | pubmed-58004322018-02-08 Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation Yan, Zhenzhen Shi, Haihong Zhu, Rongrong Li, Lele Qin, Bai Kang, Lihua Chen, Hui Guan, Huaijin Mol Vis Research Article PURPOSE: Age-related macular degeneration (AMD) is the leading cause of central visual loss among patients over the age of 55 years worldwide. Neovascular-type AMD (nAMD) accounts for approximately 10% of patients with AMD and is characterized by choroidal neovascularization (CNV). The proliferation of choroidal endothelial cells (CECs) is one important step in the formation of new vessels. Transcriptional coactivator Yes-associated protein (YAP) can promote the proliferation of multiple cancer cells, corneal endothelial cells, and vascular smooth muscle cells, which participate in angiogenesis. This study intends to reveal the expression and functions of YAP during the CNV process. METHODS: In the study, a mouse CNV model was generated by laser photocoagulation. YAP expression was detected with western blotting and immunohistochemistry. YAP siRNA and ranibizumab, a VEGF monoclonal antibody, were injected intravitreally in CNV mice. The YAP and VEGF expression levels after injection were detected with western blotting. The incidence and leakage area of CNV were measured with fundus fluorescein angiography, choroidal flat mounting, and hematoxylin and eosin (HE) staining. Immunofluorescent double staining was used to detect YAP cellular localization with CD31 (an endothelial cell marker) antibody. Proliferating cell nuclear antigen (PCNA) expression in CNV mice without or with YAP siRNA intravitreal injection and the colocalization of PCNA and CD31 were measured with western blotting and immunofluorescent double staining, respectively. RESULTS: YAP expression increased following laser exposure, in accordance with vascular endothelial growth factor (VEGF) expression. YAP siRNA and ranibizumab decreased VEGF expression and the incidence and leakage area of CNV. YAP was localized in the vascular endothelium within the CNV site. Additionally, after laser exposure, YAP siRNA inhibited the increased expression of PCNA, which was colocalized with endothelial cells. CONCLUSIONS: This study showed that YAP upregulation promoted CNV formation by upregulating the proliferation of endothelial cells, providing evidence for the molecular mechanisms of CNV and suggesting a novel molecular target for nAMD treatment. Molecular Vision 2018-01-31 /pmc/articles/PMC5800432/ /pubmed/29422766 Text en Copyright © 2018 Molecular Vision. http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed. |
spellingShingle | Research Article Yan, Zhenzhen Shi, Haihong Zhu, Rongrong Li, Lele Qin, Bai Kang, Lihua Chen, Hui Guan, Huaijin Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation |
title | Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation |
title_full | Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation |
title_fullStr | Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation |
title_full_unstemmed | Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation |
title_short | Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation |
title_sort | inhibition of yap ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5800432/ https://www.ncbi.nlm.nih.gov/pubmed/29422766 |
work_keys_str_mv | AT yanzhenzhen inhibitionofyapameliorateschoroidalneovascularizationviainhibitingendothelialcellproliferation AT shihaihong inhibitionofyapameliorateschoroidalneovascularizationviainhibitingendothelialcellproliferation AT zhurongrong inhibitionofyapameliorateschoroidalneovascularizationviainhibitingendothelialcellproliferation AT lilele inhibitionofyapameliorateschoroidalneovascularizationviainhibitingendothelialcellproliferation AT qinbai inhibitionofyapameliorateschoroidalneovascularizationviainhibitingendothelialcellproliferation AT kanglihua inhibitionofyapameliorateschoroidalneovascularizationviainhibitingendothelialcellproliferation AT chenhui inhibitionofyapameliorateschoroidalneovascularizationviainhibitingendothelialcellproliferation AT guanhuaijin inhibitionofyapameliorateschoroidalneovascularizationviainhibitingendothelialcellproliferation |