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High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner

We aimed to investigate the effects of different concentrations of vascular endothelial growth factor (VEGF) on the extracellular matrix (ECM) and fibrotic proteins in human trabecular meshwork (TM) cells. We also explored how the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-bi...

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Autores principales: Sung, Mi Sun, Kim, So Young, Eom, Gwang Hyeon, Park, Sang Woo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253844/
https://www.ncbi.nlm.nih.gov/pubmed/37298577
http://dx.doi.org/10.3390/ijms24119625
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author Sung, Mi Sun
Kim, So Young
Eom, Gwang Hyeon
Park, Sang Woo
author_facet Sung, Mi Sun
Kim, So Young
Eom, Gwang Hyeon
Park, Sang Woo
author_sort Sung, Mi Sun
collection PubMed
description We aimed to investigate the effects of different concentrations of vascular endothelial growth factor (VEGF) on the extracellular matrix (ECM) and fibrotic proteins in human trabecular meshwork (TM) cells. We also explored how the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway modulates VEGF-induced fibrosis. We determined cross-linked actin network (CLAN) formation using TM cells. Changes in fibrotic and ECM protein expression were determined. High VEGF concentrations (10 and 30 ng/mL) increased TAZ and decreased p-TAZ/TAZ expression in TM cells. Western blotting and real-time PCR revealed no YAP expression changes. Fibrotic and ECM protein expression decreased at low VEGF concentrations (1 and 10 ρg/mL) and significantly increased at high VEGF concentrations (10 and 30 ng/mL). CLAN formation increased in TM cells treated with high VEGF concentrations. Moreover, TAZ inhibition by verteporfin (1 μM) rescued TM cells from high-VEGF-concentration-induced fibrosis. Low VEGF concentrations reduced fibrotic changes, whereas high VEGF concentrations accelerated fibrosis and CLAN formations in TM cells in a TAZ-dependent manner. These findings reflect the dose-dependent influences of VEGF on TM cells. Moreover, TAZ inhibition might be a therapeutic target for VEGF-induced TM dysfunction.
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spelling pubmed-102538442023-06-10 High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner Sung, Mi Sun Kim, So Young Eom, Gwang Hyeon Park, Sang Woo Int J Mol Sci Article We aimed to investigate the effects of different concentrations of vascular endothelial growth factor (VEGF) on the extracellular matrix (ECM) and fibrotic proteins in human trabecular meshwork (TM) cells. We also explored how the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway modulates VEGF-induced fibrosis. We determined cross-linked actin network (CLAN) formation using TM cells. Changes in fibrotic and ECM protein expression were determined. High VEGF concentrations (10 and 30 ng/mL) increased TAZ and decreased p-TAZ/TAZ expression in TM cells. Western blotting and real-time PCR revealed no YAP expression changes. Fibrotic and ECM protein expression decreased at low VEGF concentrations (1 and 10 ρg/mL) and significantly increased at high VEGF concentrations (10 and 30 ng/mL). CLAN formation increased in TM cells treated with high VEGF concentrations. Moreover, TAZ inhibition by verteporfin (1 μM) rescued TM cells from high-VEGF-concentration-induced fibrosis. Low VEGF concentrations reduced fibrotic changes, whereas high VEGF concentrations accelerated fibrosis and CLAN formations in TM cells in a TAZ-dependent manner. These findings reflect the dose-dependent influences of VEGF on TM cells. Moreover, TAZ inhibition might be a therapeutic target for VEGF-induced TM dysfunction. MDPI 2023-06-01 /pmc/articles/PMC10253844/ /pubmed/37298577 http://dx.doi.org/10.3390/ijms24119625 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sung, Mi Sun
Kim, So Young
Eom, Gwang Hyeon
Park, Sang Woo
High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner
title High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner
title_full High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner
title_fullStr High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner
title_full_unstemmed High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner
title_short High VEGF Concentrations Accelerate Human Trabecular Meshwork Fibrosis in a TAZ-Dependent Manner
title_sort high vegf concentrations accelerate human trabecular meshwork fibrosis in a taz-dependent manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10253844/
https://www.ncbi.nlm.nih.gov/pubmed/37298577
http://dx.doi.org/10.3390/ijms24119625
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