{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:02:19Z","timestamp":1782230539222,"version":"3.54.5"},"reference-count":66,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T00:00:00Z","timestamp":1568937600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K09965"],"award-info":[{"award-number":["19K09965"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2013Rho 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\u2013Rho 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\u2013Rho cascade was observed in pterygium tissue. Additionally, in vitro examination showed S1P\u2013rho 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.<\/jats:p>","DOI":"10.3390\/ijms20194670","type":"journal-article","created":{"date-parts":[[2019,9,20]],"date-time":"2019-09-20T10:48:14Z","timestamp":1568976494000},"page":"4670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Activation of the Sphingosine 1 Phosphate\u2013Rho Pathway in Pterygium and in Ultraviolet-Irradiated Normal Conjunctiva"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2275-6285","authenticated-orcid":false,"given":"Nozomi","family":"Igarashi","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Honjo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Fujishiro","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Toyono","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1288-2798","authenticated-orcid":false,"given":"Takashi","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan"},{"name":"Miyata eye hospital, Miyazaki 885-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosai","family":"Mori","sequence":"additional","affiliation":[{"name":"Miyata eye hospital, Miyazaki 885-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Miyata","sequence":"additional","affiliation":[{"name":"Miyata eye hospital, Miyazaki 885-0051, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideru","family":"Obinata","sequence":"additional","affiliation":[{"name":"Gunma University Initiative for Advanced Research (GIAR), Gunma 371-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6810-0583","authenticated-orcid":false,"given":"Makoto","family":"Aihara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.preteyeres.2004.02.002","article-title":"Pathogenesis of pterygia: Role of cytokines, growth factors, and matrix metalloproteinases","volume":"23","author":"Chui","year":"2004","journal-title":"Prog. 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