J Korean Ophthalmol Soc.  2023 Jun;64(6):522-531. 10.3341/jkos.2023.64.6.522.

Effects of Vascular Endothelial Growth Factor on YAP/TAZ Signaling in Trabecular Meshwork Cells

• Kim SY
• Sung MS
• Park SW

• KMID: 2542873
• DOI: http://doi.org/10.3341/jkos.2023.64.6.522

Abstract

Purpose
To investigate the effects of vascular endothelial growth factor (VEGF) on yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding motif (TAZ), a Hippo pathway-related transcription factor, and the role of YAP/TAZ induced by trabecular meshwork stimulation.
Methods
Human trabecular meshwork cells were cultured and treated with various VEGF concentrations to verify cell cytotoxicity using the CCK-8 solution. Transforming growth factor β-2 (TGFβ2; 5 ng/mL) and VEGF (30 ng/mL) were applied and YAP/TAZ expression was assessed by western blotting, reverse transcription quantitative polymerase chain reaction and immunocytochemistry. Fibronectin, collagen 1, and myocilin expression were also assessed by western blotting. The cells were stained using Alexa Fluor 488-phalloidin to observe F-actin changes.
Results
YAP and TAZ expression increased following TGFβ2 and VEGF treatment for 24 hours. Fibronectin and collagen 1 increased significantly in all three treatment groups, while myocilin increased in the TGFβ2 and TGFβ2+VEGF groups. The F-actin staining showed increased cross-linking in the trabecular meshwork cells.
Conclusions
VEGF induced YAP/TAZ signaling and increased trabecular meshwork cell fibrosis. Based on the functional changes caused by VEGF, it is suggested that VEGF and YAP/TAZ may increase aqueous humor outflow resistance in trabecular meshwork cells.

Keyword

Hippo pathway, Trabecular meshwork, Vascular endothelial growth factor, YAP/TAZ