{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T02:12:41Z","timestamp":1776132761020,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research, Development and Innovation Office","award":["OTKA-K135398"],"award-info":[{"award-number":["OTKA-K135398"]}]},{"name":"National Research, Development and Innovation Office","award":["LP2021-3\/2021"],"award-info":[{"award-number":["LP2021-3\/2021"]}]},{"name":"National Research, Development and Innovation Office","award":["TKP2021-EGA-24"],"award-info":[{"award-number":["TKP2021-EGA-24"]}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["OTKA-K135398"],"award-info":[{"award-number":["OTKA-K135398"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["LP2021-3\/2021"],"award-info":[{"award-number":["LP2021-3\/2021"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003825","name":"Hungarian Academy of Sciences","doi-asserted-by":"publisher","award":["TKP2021-EGA-24"],"award-info":[{"award-number":["TKP2021-EGA-24"]}],"id":[{"id":"10.13039\/501100003825","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","award":["OTKA-K135398"],"award-info":[{"award-number":["OTKA-K135398"]}]},{"name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","award":["LP2021-3\/2021"],"award-info":[{"award-number":["LP2021-3\/2021"]}]},{"name":"Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund","award":["TKP2021-EGA-24"],"award-info":[{"award-number":["TKP2021-EGA-24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary open-angle glaucoma remains a global issue, lacking a definitive treatment. Increased intraocular pressure (IOP) is considered the primary risk factor of the disease and it can be caused by fibrotic-like changes in the trabecular meshwork (TM) such as increased tissue stiffness and outflow resistance. Previously, we demonstrated that the sigma-1 receptor (S1R) agonist fluvoxamine (FLU) has anti-fibrotic properties in the kidney and lung. In this study, the localization of the S1R in TM cells was determined, and the anti-fibrotic efficacy of FLU was examined in both mouse and human TM cells. Treatment with FLU reduced the F-actin rearrangement, inhibited cell proliferation and migration induced by the platelet-derived growth factor and decreased the levels of fibrotic proteins. The protective role of the S1R in fibrosis was confirmed by a more pronounced increase in alpha smooth muscle actin and F-actin bundle and clump formation in primary mouse S1R knockout TM cells. Furthermore, FLU demonstrated its protective effects by increasing the production of nitric oxide and facilitating the degradation of the extracellular matrix through the elevation of cathepsin K. These findings suggest that the S1R could be a novel target for the development of anti-fibrotic drugs and offer a new therapeutic approach for glaucoma.<\/jats:p>","DOI":"10.3390\/ijms241411646","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T21:20:14Z","timestamp":1689801614000},"page":"11646","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Sigma-1 Receptor Agonist Fluvoxamine Ameliorates Fibrotic Response of Trabecular Meshwork Cells"],"prefix":"10.3390","volume":"24","author":[{"given":"Judit","family":"Hodrea","sequence":"first","affiliation":[{"name":"MTA-SE Lend\u00fclet \u201cMomentum\u201d Diabetes Research Group, Semmelweis University, 1083 Budapest, Hungary"},{"name":"Pediatric Center, MTA Center of Excellence, Faculty of Medicine, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-0871","authenticated-orcid":false,"given":"Minh Ngoc","family":"Tran","sequence":"additional","affiliation":[{"name":"MTA-SE Lend\u00fclet \u201cMomentum\u201d Diabetes Research Group, Semmelweis University, 1083 Budapest, Hungary"},{"name":"Pediatric Center, MTA Center of Excellence, Faculty of Medicine, Semmelweis University, 1083 Budapest, Hungary"},{"name":"Department of Biochemistry, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 72712, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Balazs","family":"Besztercei","sequence":"additional","affiliation":[{"name":"Institute of Clinical Experimental Research, Semmelweis University, 1094 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timea","family":"Medveczki","sequence":"additional","affiliation":[{"name":"MTA-SE Lend\u00fclet \u201cMomentum\u201d Diabetes Research Group, Semmelweis University, 1083 Budapest, Hungary"},{"name":"Pediatric Center, MTA Center of Excellence, Faculty of Medicine, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7321-9861","authenticated-orcid":false,"given":"Attila J.","family":"Szabo","sequence":"additional","affiliation":[{"name":"Pediatric Center, MTA Center of Excellence, Faculty of Medicine, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6149-2385","authenticated-orcid":false,"given":"Laszlo","family":"\u0150rfi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Semmelweis University, 1092 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5763-0482","authenticated-orcid":false,"given":"Illes","family":"Kovacs","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Semmelweis University, 1085 Budapest, Hungary"},{"name":"Department of Clinical Ophthalmology, Faculty of Health Sciences, Semmelweis University, 1085 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Fekete","sequence":"additional","affiliation":[{"name":"MTA-SE Lend\u00fclet \u201cMomentum\u201d Diabetes Research Group, Semmelweis University, 1083 Budapest, Hungary"},{"name":"Pediatric Center, MTA Center of Excellence, Faculty of Medicine, Semmelweis University, 1083 Budapest, Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1164\/rccm.200906-0964OC","article-title":"Imatinib treatment for idiopathic pulmonary fibrosis: Randomized placebo-controlled trial results","volume":"181","author":"Daniels","year":"2010","journal-title":"Am. 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