Autotaxin May Have Lysophosphatidic Acid-Unrelated Effects on Three-Dimension (3D) Cultured Human Trabecular Meshwork (HTM) Cells

Purpose: The objective of the current study was to evaluate the effects of the autotaxin (ATX)–lysophosphatidic acid (LPA) signaling axis on the human trabecular meshwork (HTM) in two-dimensional (2D) and three-dimensional (3D) cultures of HTM cells. Methods: The effects were characterized by transe...

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Autores principales: Megumi Watanabe, Masato Furuhashi, Yuri Tsugeno, Yosuke Ida, Fumihito Hikage, Hiroshi Ohguro
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:0b6e601ba96243278ae17eab9824af7a2021-11-11T17:26:22ZAutotaxin May Have Lysophosphatidic Acid-Unrelated Effects on Three-Dimension (3D) Cultured Human Trabecular Meshwork (HTM) Cells10.3390/ijms2221120391422-00671661-6596https://doaj.org/article/0b6e601ba96243278ae17eab9824af7a2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/12039https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Purpose: The objective of the current study was to evaluate the effects of the autotaxin (ATX)–lysophosphatidic acid (LPA) signaling axis on the human trabecular meshwork (HTM) in two-dimensional (2D) and three-dimensional (3D) cultures of HTM cells. Methods: The effects were characterized by transendothelial electrical resistance (TEER) and FITC-dextran permeability (2D), measurements of size and stiffness (3D), and the expression of several genes, including extracellular matrix (ECM) molecules, their modulators, and endoplasmic reticulum (ER) stress-related factors. Results: A one-day exposure to 200 nM LPA induced significant down-sizing effects of the 3D HTM spheroids, and these effects were enhanced slightly on longer exposure. The TEER and FITC-dextran permeability data indicate that LPA induced an increase in the barrier function of the 2D HTM monolayers. A one-day exposure to a 2 mg/L solution of ATX also resulted in a significant decrease in the sizes of the 3D HTM spheroids, and an increase in stiffness was also observed. The gene expression of several ECMs, their regulators and ER-stress related factors by the 3D HTM spheroids were altered by both ATX and LPA, but in different manners. Conclusions: The findings presented herein suggest that ATX may have additional roles in the human TM, in addition to the ATX–LPA signaling axis.Megumi WatanabeMasato FuruhashiYuri TsugenoYosuke IdaFumihito HikageHiroshi OhguroMDPI AGarticle3D spheroid culturehuman trabecular meshwork (HTM)autotaxinlysophosphatidic acidBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12039, p 12039 (2021)
institution DOAJ
collection DOAJ
language EN
topic 3D spheroid culture
human trabecular meshwork (HTM)
autotaxin
lysophosphatidic acid
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle 3D spheroid culture
human trabecular meshwork (HTM)
autotaxin
lysophosphatidic acid
Biology (General)
QH301-705.5
Chemistry
QD1-999
Megumi Watanabe
Masato Furuhashi
Yuri Tsugeno
Yosuke Ida
Fumihito Hikage
Hiroshi Ohguro
Autotaxin May Have Lysophosphatidic Acid-Unrelated Effects on Three-Dimension (3D) Cultured Human Trabecular Meshwork (HTM) Cells
description Purpose: The objective of the current study was to evaluate the effects of the autotaxin (ATX)–lysophosphatidic acid (LPA) signaling axis on the human trabecular meshwork (HTM) in two-dimensional (2D) and three-dimensional (3D) cultures of HTM cells. Methods: The effects were characterized by transendothelial electrical resistance (TEER) and FITC-dextran permeability (2D), measurements of size and stiffness (3D), and the expression of several genes, including extracellular matrix (ECM) molecules, their modulators, and endoplasmic reticulum (ER) stress-related factors. Results: A one-day exposure to 200 nM LPA induced significant down-sizing effects of the 3D HTM spheroids, and these effects were enhanced slightly on longer exposure. The TEER and FITC-dextran permeability data indicate that LPA induced an increase in the barrier function of the 2D HTM monolayers. A one-day exposure to a 2 mg/L solution of ATX also resulted in a significant decrease in the sizes of the 3D HTM spheroids, and an increase in stiffness was also observed. The gene expression of several ECMs, their regulators and ER-stress related factors by the 3D HTM spheroids were altered by both ATX and LPA, but in different manners. Conclusions: The findings presented herein suggest that ATX may have additional roles in the human TM, in addition to the ATX–LPA signaling axis.
format article
author Megumi Watanabe
Masato Furuhashi
Yuri Tsugeno
Yosuke Ida
Fumihito Hikage
Hiroshi Ohguro
author_facet Megumi Watanabe
Masato Furuhashi
Yuri Tsugeno
Yosuke Ida
Fumihito Hikage
Hiroshi Ohguro
author_sort Megumi Watanabe
title Autotaxin May Have Lysophosphatidic Acid-Unrelated Effects on Three-Dimension (3D) Cultured Human Trabecular Meshwork (HTM) Cells
title_short Autotaxin May Have Lysophosphatidic Acid-Unrelated Effects on Three-Dimension (3D) Cultured Human Trabecular Meshwork (HTM) Cells
title_full Autotaxin May Have Lysophosphatidic Acid-Unrelated Effects on Three-Dimension (3D) Cultured Human Trabecular Meshwork (HTM) Cells
title_fullStr Autotaxin May Have Lysophosphatidic Acid-Unrelated Effects on Three-Dimension (3D) Cultured Human Trabecular Meshwork (HTM) Cells
title_full_unstemmed Autotaxin May Have Lysophosphatidic Acid-Unrelated Effects on Three-Dimension (3D) Cultured Human Trabecular Meshwork (HTM) Cells
title_sort autotaxin may have lysophosphatidic acid-unrelated effects on three-dimension (3d) cultured human trabecular meshwork (htm) cells
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/0b6e601ba96243278ae17eab9824af7a
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