YAP and TAZ mediate steroid-induced alterations in the trabecular meshwork cytoskeleton in human trabecular meshwork cells

Peng,Jie; Wang,Hailian; Wang,Xin; Sun,Minghan; Deng,Shaoping; Wang,Yi

doi:10.3892/ijmm.2017.3207

YAP and TAZ mediate steroid-induced alterations in the trabecular meshwork cytoskeleton in human trabecular meshwork cells

Authors:
- Jie Peng
- Hailian Wang
- Xin Wang
- Minghan Sun
- Shaoping Deng
- Yi Wang
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Affiliations: Department of Ophthalmology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China, Institute of Organ Transplantation, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China, Department of Biomedical Engineering, Medical School of the University of Electronic Science and Technology of China, Chengdu, Sichuan 610054, P.R. China, Department of Gynecology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China
Published online on: October 23, 2017 https://doi.org/10.3892/ijmm.2017.3207
Pages: 164-172
Copyright: © Peng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Primary open angle glaucoma is an important type of glaucoma as it is one of the most common causes of blindness. Previous studies have demonstrated that in glaucomatous patients, the human trabecular meshwork (HTM) is markedly stiffened. The purpose of the present study was to determine the regulatory role of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in HTM cells. Primary HTM cells were cultured with different concentrations of dexamethasone (DEX), and the expression levels of YAP and TAZ were evaluated using reverse transcription-quantitative polymerase chain reaction and western blotting. The results revealed that DEX increased the expression of YAP and TAZ in a dose-dependent manner. In addition, the western blot analysis of cytoskeleton-associated proteins revealed that the inhibition of YAP and/or TAZ using small interfering RNA resulted in the increased expression of collagen I, and decreased expression of fibronectin, laminin and collagen IV. The expression of β-catenin, a key protein in the Wnt pathway, was also observed to be regulated by YAP and TAZ. A 5-ethynyl-2'-deoxyuridine staining assay indicated that YAP and TAZ induced the proliferation of HTM cells. The investigation of cross-linked actin network formation by the HTM cells demonstrated that the knockdown of YAP and TAZ genes rescued HTM cells from cytoskeletal reorganization. Furthermore, functional evaluation of a HTM cell monolayer using a permeability assay demonstrated that the inhibition of YAP and TAZ attenuated the DEX-induced impairment of permeability. These findings suggest that YAP and TAZ play pivotal roles in the DEX-induced cytoskeletal changes of HTM cells, and reveal novel potential mechanisms for the development and progression of glaucoma.

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