Pan-ROCK and ROCK2 Inhibitors Affect Dexamethasone-Treated 2D- and 3D-Cultured Human Trabecular Meshwork (HTM) Cells in Opposite Manners

Effects of a pan-ROCK-inhibitor, ripasudil (Rip), and a ROCK2 inhibitor, KD025 on dexamethasone (DEX)-treated human trabecular meshwork (HTM) cells as a model of steroid-induced glaucoma were investigated. In the presence of Rip or KD025, DEX-treated HTM cells were subjected to permeability analysis...

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Autores principales:	Megumi Watanabe, Yosuke Ida, Masato Furuhashi, Yuri Tsugeno, Fumihito Hikage, Hiroshi Ohguro
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	3D spheroid cultures human trabecular meshwork (HTM) Rho-associated coiled-coil containing protein kinase (ROCK) ripasudil KD025 dexamethasone Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/87169559e7f3417f91f53c735e7bf2e0
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spelling	oai:doaj.org-article:87169559e7f3417f91f53c735e7bf2e02021-11-11T18:24:35ZPan-ROCK and ROCK2 Inhibitors Affect Dexamethasone-Treated 2D- and 3D-Cultured Human Trabecular Meshwork (HTM) Cells in Opposite Manners10.3390/molecules262163821420-3049https://doaj.org/article/87169559e7f3417f91f53c735e7bf2e02021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6382https://doaj.org/toc/1420-3049Effects of a pan-ROCK-inhibitor, ripasudil (Rip), and a ROCK2 inhibitor, KD025 on dexamethasone (DEX)-treated human trabecular meshwork (HTM) cells as a model of steroid-induced glaucoma were investigated. In the presence of Rip or KD025, DEX-treated HTM cells were subjected to permeability analysis of 2D monolayer by transendothelial electrical resistance (TEER) and FITC–dextran permeability, physical properties, size and stiffness analysis (3D), and qPCR of extracellular matrix (ECM), and their modulators. DEX resulted in a significant increase in the permeability, as well as a large and stiff 3D spheroid, and those effects were inhibited by Rip. In contrast, KD025 exerted opposite effects on the physical properties (down-sizing and softening). Furthermore, DEX induced several changes of gene expressions of ECM and their modulators were also modulated differently by Rip and KD025. The present findings indicate that Rip and KD025 induced opposite effects toward 2D and 3D cell cultures of DEX-treated HTM cells.Megumi WatanabeYosuke IdaMasato FuruhashiYuri TsugenoFumihito HikageHiroshi OhguroMDPI AGarticle3D spheroid cultureshuman trabecular meshwork (HTM)Rho-associated coiled-coil containing protein kinase (ROCK)ripasudilKD025dexamethasoneOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6382, p 6382 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	3D spheroid cultures human trabecular meshwork (HTM) Rho-associated coiled-coil containing protein kinase (ROCK) ripasudil KD025 dexamethasone Organic chemistry QD241-441
spellingShingle	3D spheroid cultures human trabecular meshwork (HTM) Rho-associated coiled-coil containing protein kinase (ROCK) ripasudil KD025 dexamethasone Organic chemistry QD241-441 Megumi Watanabe Yosuke Ida Masato Furuhashi Yuri Tsugeno Fumihito Hikage Hiroshi Ohguro Pan-ROCK and ROCK2 Inhibitors Affect Dexamethasone-Treated 2D- and 3D-Cultured Human Trabecular Meshwork (HTM) Cells in Opposite Manners
description	Effects of a pan-ROCK-inhibitor, ripasudil (Rip), and a ROCK2 inhibitor, KD025 on dexamethasone (DEX)-treated human trabecular meshwork (HTM) cells as a model of steroid-induced glaucoma were investigated. In the presence of Rip or KD025, DEX-treated HTM cells were subjected to permeability analysis of 2D monolayer by transendothelial electrical resistance (TEER) and FITC–dextran permeability, physical properties, size and stiffness analysis (3D), and qPCR of extracellular matrix (ECM), and their modulators. DEX resulted in a significant increase in the permeability, as well as a large and stiff 3D spheroid, and those effects were inhibited by Rip. In contrast, KD025 exerted opposite effects on the physical properties (down-sizing and softening). Furthermore, DEX induced several changes of gene expressions of ECM and their modulators were also modulated differently by Rip and KD025. The present findings indicate that Rip and KD025 induced opposite effects toward 2D and 3D cell cultures of DEX-treated HTM cells.
format	article
author	Megumi Watanabe Yosuke Ida Masato Furuhashi Yuri Tsugeno Fumihito Hikage Hiroshi Ohguro
author_facet	Megumi Watanabe Yosuke Ida Masato Furuhashi Yuri Tsugeno Fumihito Hikage Hiroshi Ohguro
author_sort	Megumi Watanabe
title	Pan-ROCK and ROCK2 Inhibitors Affect Dexamethasone-Treated 2D- and 3D-Cultured Human Trabecular Meshwork (HTM) Cells in Opposite Manners
title_short	Pan-ROCK and ROCK2 Inhibitors Affect Dexamethasone-Treated 2D- and 3D-Cultured Human Trabecular Meshwork (HTM) Cells in Opposite Manners
title_full	Pan-ROCK and ROCK2 Inhibitors Affect Dexamethasone-Treated 2D- and 3D-Cultured Human Trabecular Meshwork (HTM) Cells in Opposite Manners
title_fullStr	Pan-ROCK and ROCK2 Inhibitors Affect Dexamethasone-Treated 2D- and 3D-Cultured Human Trabecular Meshwork (HTM) Cells in Opposite Manners
title_full_unstemmed	Pan-ROCK and ROCK2 Inhibitors Affect Dexamethasone-Treated 2D- and 3D-Cultured Human Trabecular Meshwork (HTM) Cells in Opposite Manners
title_sort	pan-rock and rock2 inhibitors affect dexamethasone-treated 2d- and 3d-cultured human trabecular meshwork (htm) cells in opposite manners
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/87169559e7f3417f91f53c735e7bf2e0
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Pan-ROCK and ROCK2 Inhibitors Affect Dexamethasone-Treated 2D- and 3D-Cultured Human Trabecular Meshwork (HTM) Cells in Opposite Manners

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