YAP/TAZ Promote Fibrotic Activity in Human Trabecular Meshwork Cells by Sensing Cytoskeleton Structure Alternation

Trabecular meshwork (TM) is the main channel of aqueous humor (AH) outflow and the crucial tissue responsible for intraocular pressure (IOP) regulation. The aberrant fibrotic activity of human TM (HTM) cells is thought to be partially responsible for the increased resistance to AH outflow and elevat...

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Main Authors: Shan Huang, Zhicheng Liu, Xiuqing Qian, Lin Li, Haixia Zhang, Shanshan Li
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Chemosensors
Subjects:
Online Access:https://www.mdpi.com/2227-9040/10/7/235
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author Shan Huang
Zhicheng Liu
Xiuqing Qian
Lin Li
Haixia Zhang
Shanshan Li
Zhicheng Liu
author_facet Shan Huang
Zhicheng Liu
Xiuqing Qian
Lin Li
Haixia Zhang
Shanshan Li
Zhicheng Liu
author_sort Shan Huang
collection DOAJ
description Trabecular meshwork (TM) is the main channel of aqueous humor (AH) outflow and the crucial tissue responsible for intraocular pressure (IOP) regulation. The aberrant fibrotic activity of human TM (HTM) cells is thought to be partially responsible for the increased resistance to AH outflow and elevated IOP. This study aimed to identify the TM cell fibrotic activity biomarker and illustrate the mechanisms of fibrotic activity regulation in HTM cells. We used TGFβ2-treated HTM cells and detected the changes in the cytoskeletal structure, the Yes-associated protein (YAP) and its transcriptional co-activator with PDZ-binding domain (TAZ) activation, and the expression levels of the fibrosis-related proteins Collagen I and α-SMA in HTM cells by immunofluorescence staining or western bolt analyses. The expression of YAP was inhibited using siRNA transfection. The results showed that the expression levels of YAP/TAZ and the fibrosis-related proteins Collagen I and α-SMA in HTM cells were elevated under TGF-β2 treatment, which was correlated with the structural change of the cellular F-actin cytoskeleton. Furthermore, the inhibition of YAP decreased the expression of connective tissue growth factor (CTGF), Collagen I, and α-SMA in HTM cells. These findings demonstrate that YAP/TAZ are potential biomarkers in evaluating the TM cell fibrotic activity, and it could sense cytoskeletal structure cues and regulate the fibrotic activity of TM cells.
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spelling doaj.art-67b48f086bda467e8bc875a2620ce4fd2023-12-03T14:50:12ZengMDPI AGChemosensors2227-90402022-06-0110723510.3390/chemosensors10070235YAP/TAZ Promote Fibrotic Activity in Human Trabecular Meshwork Cells by Sensing Cytoskeleton Structure AlternationShan Huang0Zhicheng Liu1Xiuqing Qian2Lin Li3Haixia Zhang4Shanshan Li5Zhicheng Liu6School of Biomedical Engineering, Capital Medical University, Beijing 100069, ChinaSchool of Biomedical Engineering, Capital Medical University, Beijing 100069, ChinaSchool of Biomedical Engineering, Capital Medical University, Beijing 100069, ChinaSchool of Biomedical Engineering, Capital Medical University, Beijing 100069, ChinaSchool of Biomedical Engineering, Capital Medical University, Beijing 100069, ChinaSchool of Biomedical Engineering, Capital Medical University, Beijing 100069, ChinaSchool of Biomedical Engineering, Capital Medical University, Beijing 100069, ChinaTrabecular meshwork (TM) is the main channel of aqueous humor (AH) outflow and the crucial tissue responsible for intraocular pressure (IOP) regulation. The aberrant fibrotic activity of human TM (HTM) cells is thought to be partially responsible for the increased resistance to AH outflow and elevated IOP. This study aimed to identify the TM cell fibrotic activity biomarker and illustrate the mechanisms of fibrotic activity regulation in HTM cells. We used TGFβ2-treated HTM cells and detected the changes in the cytoskeletal structure, the Yes-associated protein (YAP) and its transcriptional co-activator with PDZ-binding domain (TAZ) activation, and the expression levels of the fibrosis-related proteins Collagen I and α-SMA in HTM cells by immunofluorescence staining or western bolt analyses. The expression of YAP was inhibited using siRNA transfection. The results showed that the expression levels of YAP/TAZ and the fibrosis-related proteins Collagen I and α-SMA in HTM cells were elevated under TGF-β2 treatment, which was correlated with the structural change of the cellular F-actin cytoskeleton. Furthermore, the inhibition of YAP decreased the expression of connective tissue growth factor (CTGF), Collagen I, and α-SMA in HTM cells. These findings demonstrate that YAP/TAZ are potential biomarkers in evaluating the TM cell fibrotic activity, and it could sense cytoskeletal structure cues and regulate the fibrotic activity of TM cells.https://www.mdpi.com/2227-9040/10/7/235trabecular meshworkextracellular matrixfibrotic activitycytoskeleton
spellingShingle Shan Huang
Zhicheng Liu
Xiuqing Qian
Lin Li
Haixia Zhang
Shanshan Li
Zhicheng Liu
YAP/TAZ Promote Fibrotic Activity in Human Trabecular Meshwork Cells by Sensing Cytoskeleton Structure Alternation
Chemosensors
trabecular meshwork
extracellular matrix
fibrotic activity
cytoskeleton
title YAP/TAZ Promote Fibrotic Activity in Human Trabecular Meshwork Cells by Sensing Cytoskeleton Structure Alternation
title_full YAP/TAZ Promote Fibrotic Activity in Human Trabecular Meshwork Cells by Sensing Cytoskeleton Structure Alternation
title_fullStr YAP/TAZ Promote Fibrotic Activity in Human Trabecular Meshwork Cells by Sensing Cytoskeleton Structure Alternation
title_full_unstemmed YAP/TAZ Promote Fibrotic Activity in Human Trabecular Meshwork Cells by Sensing Cytoskeleton Structure Alternation
title_short YAP/TAZ Promote Fibrotic Activity in Human Trabecular Meshwork Cells by Sensing Cytoskeleton Structure Alternation
title_sort yap taz promote fibrotic activity in human trabecular meshwork cells by sensing cytoskeleton structure alternation
topic trabecular meshwork
extracellular matrix
fibrotic activity
cytoskeleton
url https://www.mdpi.com/2227-9040/10/7/235
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