Reactivities of a Prostanoid EP2 Agonist, Omidenepag, Are Useful for Distinguishing between 3D Spheroids of Human Orbital Fibroblasts without or with Graves’ Orbitopathy

Background. To obtain new insights into the activation of the thyroid-stimulating hormone (TSH) and insulin-like growth factor 1 (IGF-1) receptors in human orbital fibroblasts (n-HOFs), the effects of the prostanoid EP2 agonist, omidenepag (OMD), and a rho-associated coiled-coil-containing protein k...

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Autores principales:	Yosuke Ida, Hanae Ichioka, Masato Furuhashi, Fumihito Hikage, Megumi Watanabe, Araya Umetsu, Hiroshi Ohguro
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	prostanoid EP2 agonist ROCK inhibitor three-dimension (3D) cell culture Graves’ orbitopathy IGF-1 orbital fibroblast Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c153308afa234843a145a51e10e3f285
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spelling	oai:doaj.org-article:c153308afa234843a145a51e10e3f2852021-11-25T17:12:44ZReactivities of a Prostanoid EP2 Agonist, Omidenepag, Are Useful for Distinguishing between 3D Spheroids of Human Orbital Fibroblasts without or with Graves’ Orbitopathy10.3390/cells101131962073-4409https://doaj.org/article/c153308afa234843a145a51e10e3f2852021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3196https://doaj.org/toc/2073-4409Background. To obtain new insights into the activation of the thyroid-stimulating hormone (TSH) and insulin-like growth factor 1 (IGF-1) receptors in human orbital fibroblasts (n-HOFs), the effects of the prostanoid EP2 agonist, omidenepag (OMD), and a rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, ripasudil (Rip) were evaluated using three-dimension (3D) n-HOFs spheroids in the absence and presence of the recombinant human TSH receptor antibodies, M22 and IGF-1. Methods. The effects of 100 nM OMD or 10 μM Rip on the physical properties, size, stiffness, and mRNA expression of several extracellular matrix (ECM) molecules, their regulator, inflammatory cytokines, and endoplasmic reticulum (ER) stress-related factors were examined and compared among 3D spheroids of n-HOFs, M22-/IGF-1-activated n-HOFs and GO-related human orbital fibroblasts (GHOFs). Results. The physical properties and mRNA expressions of several genes of the 3D n-HOFs spheroids were significantly and diversely modulated by the presence of OMD or Rip. The OMD-induced effects on M22-/IGF-1-activated n-HOFs were similar to the effects caused by GHOHs, but quite different from those of n-HOFs. Conclusions. The findings presented herein indicate that the changes induced by OMD may be useful in distinguishing between n-HOFs and GHOFs.Yosuke IdaHanae IchiokaMasato FuruhashiFumihito HikageMegumi WatanabeAraya UmetsuHiroshi OhguroMDPI AGarticleprostanoid EP2 agonistROCK inhibitorthree-dimension (3D) cell cultureGraves’ orbitopathyIGF-1orbital fibroblastBiology (General)QH301-705.5ENCells, Vol 10, Iss 3196, p 3196 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	prostanoid EP2 agonist ROCK inhibitor three-dimension (3D) cell culture Graves’ orbitopathy IGF-1 orbital fibroblast Biology (General) QH301-705.5
spellingShingle	prostanoid EP2 agonist ROCK inhibitor three-dimension (3D) cell culture Graves’ orbitopathy IGF-1 orbital fibroblast Biology (General) QH301-705.5 Yosuke Ida Hanae Ichioka Masato Furuhashi Fumihito Hikage Megumi Watanabe Araya Umetsu Hiroshi Ohguro Reactivities of a Prostanoid EP2 Agonist, Omidenepag, Are Useful for Distinguishing between 3D Spheroids of Human Orbital Fibroblasts without or with Graves’ Orbitopathy
description	Background. To obtain new insights into the activation of the thyroid-stimulating hormone (TSH) and insulin-like growth factor 1 (IGF-1) receptors in human orbital fibroblasts (n-HOFs), the effects of the prostanoid EP2 agonist, omidenepag (OMD), and a rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, ripasudil (Rip) were evaluated using three-dimension (3D) n-HOFs spheroids in the absence and presence of the recombinant human TSH receptor antibodies, M22 and IGF-1. Methods. The effects of 100 nM OMD or 10 μM Rip on the physical properties, size, stiffness, and mRNA expression of several extracellular matrix (ECM) molecules, their regulator, inflammatory cytokines, and endoplasmic reticulum (ER) stress-related factors were examined and compared among 3D spheroids of n-HOFs, M22-/IGF-1-activated n-HOFs and GO-related human orbital fibroblasts (GHOFs). Results. The physical properties and mRNA expressions of several genes of the 3D n-HOFs spheroids were significantly and diversely modulated by the presence of OMD or Rip. The OMD-induced effects on M22-/IGF-1-activated n-HOFs were similar to the effects caused by GHOHs, but quite different from those of n-HOFs. Conclusions. The findings presented herein indicate that the changes induced by OMD may be useful in distinguishing between n-HOFs and GHOFs.
format	article
author	Yosuke Ida Hanae Ichioka Masato Furuhashi Fumihito Hikage Megumi Watanabe Araya Umetsu Hiroshi Ohguro
author_facet	Yosuke Ida Hanae Ichioka Masato Furuhashi Fumihito Hikage Megumi Watanabe Araya Umetsu Hiroshi Ohguro
author_sort	Yosuke Ida
title	Reactivities of a Prostanoid EP2 Agonist, Omidenepag, Are Useful for Distinguishing between 3D Spheroids of Human Orbital Fibroblasts without or with Graves’ Orbitopathy
title_short	Reactivities of a Prostanoid EP2 Agonist, Omidenepag, Are Useful for Distinguishing between 3D Spheroids of Human Orbital Fibroblasts without or with Graves’ Orbitopathy
title_full	Reactivities of a Prostanoid EP2 Agonist, Omidenepag, Are Useful for Distinguishing between 3D Spheroids of Human Orbital Fibroblasts without or with Graves’ Orbitopathy
title_fullStr	Reactivities of a Prostanoid EP2 Agonist, Omidenepag, Are Useful for Distinguishing between 3D Spheroids of Human Orbital Fibroblasts without or with Graves’ Orbitopathy
title_full_unstemmed	Reactivities of a Prostanoid EP2 Agonist, Omidenepag, Are Useful for Distinguishing between 3D Spheroids of Human Orbital Fibroblasts without or with Graves’ Orbitopathy
title_sort	reactivities of a prostanoid ep2 agonist, omidenepag, are useful for distinguishing between 3d spheroids of human orbital fibroblasts without or with graves’ orbitopathy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/c153308afa234843a145a51e10e3f285
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Reactivities of a Prostanoid EP2 Agonist, Omidenepag, Are Useful for Distinguishing between 3D Spheroids of Human Orbital Fibroblasts without or with Graves’ Orbitopathy

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