Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2

Abstract A pan-ROCK-inhibitor, ripasudil (Rip), and a ROCK2 inhibitor, KD025, were used To study the effects of Rho-associated coiled-coil containing protein kinase (ROCK)1 and 2 on two-dimensional (2D) and three-dimensional (3D) cultures of a TGFβ2-treated human trabecular meshwork (HTM) cells. In...

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Autores principales:	Megumi Watanabe, Yosuke Ida, Hiroshi Ohguro, Chiaki Ota, Fumihito Hikage
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/da156467102a4b01aed4cc8bf8e6b77d
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spelling	oai:doaj.org-article:da156467102a4b01aed4cc8bf8e6b77d2021-12-02T18:47:03ZDiverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ210.1038/s41598-021-94791-42045-2322https://doaj.org/article/da156467102a4b01aed4cc8bf8e6b77d2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94791-4https://doaj.org/toc/2045-2322Abstract A pan-ROCK-inhibitor, ripasudil (Rip), and a ROCK2 inhibitor, KD025, were used To study the effects of Rho-associated coiled-coil containing protein kinase (ROCK)1 and 2 on two-dimensional (2D) and three-dimensional (3D) cultures of a TGFβ2-treated human trabecular meshwork (HTM) cells. In the presence of 5 ng/mL TGFβ2, the effects of these inhibitors were characterized by transendothelial electrical resistance (TEER), FITC-dextran permeability, and the size and stiffness of 3D sphenoids, the expression of extracellular matrix (ECM) including collagen1, 4 and 6, and fibronectin, α-smooth muscle actin, a tissue inhibitor of metalloproteinase (TIMP)1–4, and matrix metalloproteinase (MMP)2, 9 and 14. TGFβ2 caused a significant increase in the TEER values, and decrease in FITC-dextran permeability, as well as a decrease in the sizes and stiffness of the 3D sphenoids. In the presence of ROCK inhibitors, the TGFβ2-induced effects of the TEER and FITC-dextran permeability were inhibited, especially by KD025. Rip induced a significant increase in sizes and a decrease in the stiffness of the TGFβ2-treated 3D sphenoids, although the effects of KD025 were weaker. Gene expressions of most of the ECMs, TIMP2 and MMP9 of 2D and 3D HTM cells were significantly up-regulated by TGFβ2. Those were significantly and differently modulated by Rip or KD025.Megumi WatanabeYosuke IdaHiroshi OhguroChiaki OtaFumihito HikageNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Megumi Watanabe Yosuke Ida Hiroshi Ohguro Chiaki Ota Fumihito Hikage Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2
description	Abstract A pan-ROCK-inhibitor, ripasudil (Rip), and a ROCK2 inhibitor, KD025, were used To study the effects of Rho-associated coiled-coil containing protein kinase (ROCK)1 and 2 on two-dimensional (2D) and three-dimensional (3D) cultures of a TGFβ2-treated human trabecular meshwork (HTM) cells. In the presence of 5 ng/mL TGFβ2, the effects of these inhibitors were characterized by transendothelial electrical resistance (TEER), FITC-dextran permeability, and the size and stiffness of 3D sphenoids, the expression of extracellular matrix (ECM) including collagen1, 4 and 6, and fibronectin, α-smooth muscle actin, a tissue inhibitor of metalloproteinase (TIMP)1–4, and matrix metalloproteinase (MMP)2, 9 and 14. TGFβ2 caused a significant increase in the TEER values, and decrease in FITC-dextran permeability, as well as a decrease in the sizes and stiffness of the 3D sphenoids. In the presence of ROCK inhibitors, the TGFβ2-induced effects of the TEER and FITC-dextran permeability were inhibited, especially by KD025. Rip induced a significant increase in sizes and a decrease in the stiffness of the TGFβ2-treated 3D sphenoids, although the effects of KD025 were weaker. Gene expressions of most of the ECMs, TIMP2 and MMP9 of 2D and 3D HTM cells were significantly up-regulated by TGFβ2. Those were significantly and differently modulated by Rip or KD025.
format	article
author	Megumi Watanabe Yosuke Ida Hiroshi Ohguro Chiaki Ota Fumihito Hikage
author_facet	Megumi Watanabe Yosuke Ida Hiroshi Ohguro Chiaki Ota Fumihito Hikage
author_sort	Megumi Watanabe
title	Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2
title_short	Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2
title_full	Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2
title_fullStr	Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2
title_full_unstemmed	Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2
title_sort	diverse effects of pan-rock and rock2 inhibitors on 2 d and 3d cultured human trabecular meshwork (htm) cells treated with tgfβ2
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/da156467102a4b01aed4cc8bf8e6b77d
work_keys_str_mv	AT megumiwatanabe diverseeffectsofpanrockandrock2inhibitorson2dand3dculturedhumantrabecularmeshworkhtmcellstreatedwithtgfb2 AT yosukeida diverseeffectsofpanrockandrock2inhibitorson2dand3dculturedhumantrabecularmeshworkhtmcellstreatedwithtgfb2 AT hiroshiohguro diverseeffectsofpanrockandrock2inhibitorson2dand3dculturedhumantrabecularmeshworkhtmcellstreatedwithtgfb2 AT chiakiota diverseeffectsofpanrockandrock2inhibitorson2dand3dculturedhumantrabecularmeshworkhtmcellstreatedwithtgfb2 AT fumihitohikage diverseeffectsofpanrockandrock2inhibitorson2dand3dculturedhumantrabecularmeshworkhtmcellstreatedwithtgfb2
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Diverse effects of pan-ROCK and ROCK2 inhibitors on 2 D and 3D cultured human trabecular meshwork (HTM) cells treated with TGFβ2

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