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Deficiency of Yes-Associated Protein Induces Cataract in Mice
Cataract is a major cause of blindness worldwide, its complicated and unclear etiopathogenesis limit effective therapy. Here, we found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in lens epithelial cells and Yap conditional knockout (cKO) in the lens leads to cata...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
JKL International LLC
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457047/ https://www.ncbi.nlm.nih.gov/pubmed/31011480 http://dx.doi.org/10.14336/AD.2018.0910 |
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author | He, Qing Gao, Yuhao Wang, Tongxing Zhou, Lujun Zhou, Wenxia Yuan, Zengqiang |
author_facet | He, Qing Gao, Yuhao Wang, Tongxing Zhou, Lujun Zhou, Wenxia Yuan, Zengqiang |
author_sort | He, Qing |
collection | PubMed |
description | Cataract is a major cause of blindness worldwide, its complicated and unclear etiopathogenesis limit effective therapy. Here, we found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in lens epithelial cells and Yap conditional knockout (cKO) in the lens leads to cataract. Histologically, Yap deficient lens show fewer epithelial cells, retention of nuclei and accumulation of morgagnian globules in the transitional zone and the posterior area. Mechanistically, GFAP-mediated Yap cKO leads to the reduced proliferation of epithelial cells, delayed fiber cell denucleation and increased cellular senescence in lens. Further RNA profiling analysis reveals Yap cKO results in a significant alteration in gene transcription that is involved in eye development, lens structure, inflammation, cellular proliferation and polarity. Collectively, our data reveal a novel function of Yap in the lens and links Yap deficiency with the development of cataract, making Yap a promising target for cataract therapy. |
format | Online Article Text |
id | pubmed-6457047 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | JKL International LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-64570472019-04-22 Deficiency of Yes-Associated Protein Induces Cataract in Mice He, Qing Gao, Yuhao Wang, Tongxing Zhou, Lujun Zhou, Wenxia Yuan, Zengqiang Aging Dis Original Article Cataract is a major cause of blindness worldwide, its complicated and unclear etiopathogenesis limit effective therapy. Here, we found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in lens epithelial cells and Yap conditional knockout (cKO) in the lens leads to cataract. Histologically, Yap deficient lens show fewer epithelial cells, retention of nuclei and accumulation of morgagnian globules in the transitional zone and the posterior area. Mechanistically, GFAP-mediated Yap cKO leads to the reduced proliferation of epithelial cells, delayed fiber cell denucleation and increased cellular senescence in lens. Further RNA profiling analysis reveals Yap cKO results in a significant alteration in gene transcription that is involved in eye development, lens structure, inflammation, cellular proliferation and polarity. Collectively, our data reveal a novel function of Yap in the lens and links Yap deficiency with the development of cataract, making Yap a promising target for cataract therapy. JKL International LLC 2019-04-01 /pmc/articles/PMC6457047/ /pubmed/31011480 http://dx.doi.org/10.14336/AD.2018.0910 Text en Copyright: © 2019 He et al. http://creativecommons.org/licenses/by/2.0/ 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 that the original work is properly attributed. |
spellingShingle | Original Article He, Qing Gao, Yuhao Wang, Tongxing Zhou, Lujun Zhou, Wenxia Yuan, Zengqiang Deficiency of Yes-Associated Protein Induces Cataract in Mice |
title | Deficiency of Yes-Associated Protein Induces Cataract in Mice |
title_full | Deficiency of Yes-Associated Protein Induces Cataract in Mice |
title_fullStr | Deficiency of Yes-Associated Protein Induces Cataract in Mice |
title_full_unstemmed | Deficiency of Yes-Associated Protein Induces Cataract in Mice |
title_short | Deficiency of Yes-Associated Protein Induces Cataract in Mice |
title_sort | deficiency of yes-associated protein induces cataract in mice |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457047/ https://www.ncbi.nlm.nih.gov/pubmed/31011480 http://dx.doi.org/10.14336/AD.2018.0910 |
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