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Activation of the Sphingosine 1 Phosphate–Rho Pathway in Pterygium and in Ultraviolet-Irradiated Normal Conjunctiva

Sphingosine 1 phosphate (S1P) is a bioactive lipid that regulates cellular activity, including proliferation, cytoskeletal organization, migration, and fibrosis. In this study, the potential relevance of S1P–Rho signaling in pterygium formation and the effects of ultraviolet (UV) irradiation on acti...

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Autores principales: Igarashi, Nozomi, Honjo, Megumi, Fujishiro, Takashi, Toyono, Tetsuya, Ono, Takashi, Mori, Yosai, Miyata, Kazunori, Obinata, Hideru, Aihara, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801701/
https://www.ncbi.nlm.nih.gov/pubmed/31547113
http://dx.doi.org/10.3390/ijms20194670
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author Igarashi, Nozomi
Honjo, Megumi
Fujishiro, Takashi
Toyono, Tetsuya
Ono, Takashi
Mori, Yosai
Miyata, Kazunori
Obinata, Hideru
Aihara, Makoto
author_facet Igarashi, Nozomi
Honjo, Megumi
Fujishiro, Takashi
Toyono, Tetsuya
Ono, Takashi
Mori, Yosai
Miyata, Kazunori
Obinata, Hideru
Aihara, Makoto
author_sort Igarashi, Nozomi
collection PubMed
description Sphingosine 1 phosphate (S1P) is a bioactive lipid that regulates cellular activity, including proliferation, cytoskeletal organization, migration, and fibrosis. In this study, the potential relevance of S1P–Rho signaling in pterygium formation and the effects of ultraviolet (UV) irradiation on activation of the S1P/S1P receptor axis and fibrotic responses were investigated in vitro. Expressions of the S1P2, S1P4, and S1P5 receptors were significantly higher in pterygium tissue than in normal conjunctiva, and the concentration of S1P was significantly elevated in the lysate of normal conjunctival fibroblast cell (NCFC) irradiated with UV (UV-NCFCs). RhoA activity was significantly upregulated in pterygium fibroblast cells (PFCs) and UV-NCFCs, and myosin phosphatase–Rho interacting protein (MRIP) was upregulated, and myosin phosphatase target subunit 1 (MYPT1) was downregulated in PFCs. Fibrogenic changes were significantly upregulated in both PFCs and UV-NCFCs compared to NCFCs. We found that the activation of the S1P receptor–Rho cascade was observed in pterygium tissue. Additionally, in vitro examination showed S1P–rho activation and fibrogenic changes in PFCs and UV-NCFCs. S1P elevation and the resulting upregulation of the downstream Rho signaling pathway may be important in pterygium formation; this pathway offers a potential therapeutic target for suppressing pterygium generation.
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spelling pubmed-68017012019-10-31 Activation of the Sphingosine 1 Phosphate–Rho Pathway in Pterygium and in Ultraviolet-Irradiated Normal Conjunctiva Igarashi, Nozomi Honjo, Megumi Fujishiro, Takashi Toyono, Tetsuya Ono, Takashi Mori, Yosai Miyata, Kazunori Obinata, Hideru Aihara, Makoto Int J Mol Sci Article Sphingosine 1 phosphate (S1P) is a bioactive lipid that regulates cellular activity, including proliferation, cytoskeletal organization, migration, and fibrosis. In this study, the potential relevance of S1P–Rho signaling in pterygium formation and the effects of ultraviolet (UV) irradiation on activation of the S1P/S1P receptor axis and fibrotic responses were investigated in vitro. Expressions of the S1P2, S1P4, and S1P5 receptors were significantly higher in pterygium tissue than in normal conjunctiva, and the concentration of S1P was significantly elevated in the lysate of normal conjunctival fibroblast cell (NCFC) irradiated with UV (UV-NCFCs). RhoA activity was significantly upregulated in pterygium fibroblast cells (PFCs) and UV-NCFCs, and myosin phosphatase–Rho interacting protein (MRIP) was upregulated, and myosin phosphatase target subunit 1 (MYPT1) was downregulated in PFCs. Fibrogenic changes were significantly upregulated in both PFCs and UV-NCFCs compared to NCFCs. We found that the activation of the S1P receptor–Rho cascade was observed in pterygium tissue. Additionally, in vitro examination showed S1P–rho activation and fibrogenic changes in PFCs and UV-NCFCs. S1P elevation and the resulting upregulation of the downstream Rho signaling pathway may be important in pterygium formation; this pathway offers a potential therapeutic target for suppressing pterygium generation. MDPI 2019-09-20 /pmc/articles/PMC6801701/ /pubmed/31547113 http://dx.doi.org/10.3390/ijms20194670 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Igarashi, Nozomi
Honjo, Megumi
Fujishiro, Takashi
Toyono, Tetsuya
Ono, Takashi
Mori, Yosai
Miyata, Kazunori
Obinata, Hideru
Aihara, Makoto
Activation of the Sphingosine 1 Phosphate–Rho Pathway in Pterygium and in Ultraviolet-Irradiated Normal Conjunctiva
title Activation of the Sphingosine 1 Phosphate–Rho Pathway in Pterygium and in Ultraviolet-Irradiated Normal Conjunctiva
title_full Activation of the Sphingosine 1 Phosphate–Rho Pathway in Pterygium and in Ultraviolet-Irradiated Normal Conjunctiva
title_fullStr Activation of the Sphingosine 1 Phosphate–Rho Pathway in Pterygium and in Ultraviolet-Irradiated Normal Conjunctiva
title_full_unstemmed Activation of the Sphingosine 1 Phosphate–Rho Pathway in Pterygium and in Ultraviolet-Irradiated Normal Conjunctiva
title_short Activation of the Sphingosine 1 Phosphate–Rho Pathway in Pterygium and in Ultraviolet-Irradiated Normal Conjunctiva
title_sort activation of the sphingosine 1 phosphate–rho pathway in pterygium and in ultraviolet-irradiated normal conjunctiva
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801701/
https://www.ncbi.nlm.nih.gov/pubmed/31547113
http://dx.doi.org/10.3390/ijms20194670
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