{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T15:05:10Z","timestamp":1784646310923,"version":"3.55.0"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":201,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["EY031316"],"award-info":[{"award-number":["EY031316"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK128129"],"award-info":[{"award-number":["DK128129"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001209","name":"KNIGHTS TEMPLAR EYE FOUNDATION","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001209","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Analytical Cellular Pathology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Abnormal healing of corneal injury can lead to corneal opacity, a leading cause of blindness. This process is extremely complex and involves precise interactions of multiple signaling pathways. A lack of understanding of these complex interactions provides a major challenge in developing therapeutic strategies. Both sphingosine\u20101\u2010phosphate (S1P) and transforming growth factor beta (TGF\u03b2) signaling have been associated with tissue fibrosis. The purpose of this study was to understand the interplay between S1P and TGF\u03b2 signaling in the process of corneal wound healing and fibrosis. Mice lacking the\n                    <jats:italic>Sphingosine kinase 1<\/jats:italic>\n                    gene (\n                    <jats:italic>Sphk1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and their wildtype littermates were subjected to corneal injury by alkali burn. The progress of wound healing and the expression and activation of TGF\u03b2 signaling intermediates and profibrotic proteins were measured at different days postinjury (DPI). We observed that reduction of S1P signaling in\n                    <jats:italic>Sphk1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice induced the closure of corneal epithelial layer at a faster rate than its wildtype littermates following alkali burn. Reduced activation of profibrotic proteins Smad2 and 3, along with reduced expression of Smad4 and higher expression of antifibrotic protein Smad7, was also observed in the\n                    <jats:italic>Sphk1<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice as compared to the wildtype littermates following corneal injury. Inhibition of S1P signaling by exogenous delivery of a small\u2010molecule inhibitor of sphingosine kinase 1 (SphK1) could accelerate corneal wound healing in similarly injured wildtype (\n                    <jats:italic>Sphk1<\/jats:italic>\n                    <jats:sup>+\/+<\/jats:sup>\n                    ) mice. These results suggest that S1P signaling positively influences TGF\u03b2 signaling pathways that negatively affect corneal wound healing by delaying the process and inducing fibrotic development. Thus, inhibition of S1P signaling could be an effective therapeutic option to accelerate corneal wound healing and thereby prevent corneal fibrosis\/scar formation.\n                  <\/jats:p>","DOI":"10.1155\/ancp\/6404551","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T14:53:22Z","timestamp":1784645602000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["S1P, Generated by Sphingosine Kinase 1, Negatively Affects Corneal Wound Healing Process by Activating TGF\u2010\u03b2\/Smad Pathway"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3255-6285","authenticated-orcid":false,"given":"Sandip K.","family":"Basu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E.","family":"Nicholas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley P.","family":"Hambly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataliya","family":"Lenchik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Grambergs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. J.","family":"Hollingsworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Prislovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8761-3824","authenticated-orcid":false,"given":"Dimitrios","family":"Karamichos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4489-7748","authenticated-orcid":false,"given":"Nawajes","family":"Mandal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107709"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(17)30393-5"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1115\/1.2982251"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41433-019-0736-0"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2014.08.001"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108137"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10030687"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2023.108349"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11203310"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700375"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-021-05370-2"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11152336"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/stmcls\/sxag033"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.2174\/1566524011009060565"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2017.06.005"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2020.108272"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2016.03.011"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2020.10.006"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2018.09.002"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1313189"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)67133-9"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)45447-6"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.114.1.155"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/365557a0"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/381800a0"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M502207200"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176709"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.107.07113"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.TR120000972"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157742"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-016-0178-7"},{"key":"e_1_2_11_32_2","doi-asserted-by":"publisher","DOI":"10.3390\/biology11060809"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2020.0054"},{"key":"e_1_2_11_34_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00003.2020"},{"key":"e_1_2_11_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00536-1"},{"key":"e_1_2_11_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.30235"},{"key":"e_1_2_11_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00378"},{"key":"e_1_2_11_38_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.13-0967"},{"key":"e_1_2_11_39_2","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2026.13847"},{"key":"e_1_2_11_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2023.109487"},{"key":"e_1_2_11_41_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25126560"},{"key":"e_1_2_11_42_2","doi-asserted-by":"publisher","DOI":"10.1080\/15376516.2026.2659870"},{"key":"e_1_2_11_43_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2966-6_20"},{"key":"e_1_2_11_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-2966-6_28"},{"key":"e_1_2_11_45_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11182914"},{"key":"e_1_2_11_46_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25020742"},{"key":"e_1_2_11_47_2","first-page":"114","article-title":"Evaluation and Management of Corneal Abrasions","volume":"87","author":"Wipperman J. 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