Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells
The trabecular meshwork (TM) route is the principal outflow egress of the aqueous humor. Actin cytoskeletal remodeling in the TM and extracellular matrix (ECM) deposition increase TM stiffness, outflow resistance, and elevate intraocular pressure (IOP). These alterations are strongly linked to trans...
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MDPI AG
2023-07-01
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| Online Access: | https://www.mdpi.com/2075-1729/13/7/1581 |
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| author | Minh Ngoc Tran Timea Medveczki Balazs Besztercei Gyorgy Torok Attila J. Szabo Xavier Gasull Illes Kovacs Andrea Fekete Judit Hodrea |
| author_facet | Minh Ngoc Tran Timea Medveczki Balazs Besztercei Gyorgy Torok Attila J. Szabo Xavier Gasull Illes Kovacs Andrea Fekete Judit Hodrea |
| author_sort | Minh Ngoc Tran |
| collection | DOAJ |
| description | The trabecular meshwork (TM) route is the principal outflow egress of the aqueous humor. Actin cytoskeletal remodeling in the TM and extracellular matrix (ECM) deposition increase TM stiffness, outflow resistance, and elevate intraocular pressure (IOP). These alterations are strongly linked to transforming growth factor-β2 (TGFβ2), a known profibrotic cytokine that is markedly elevated in the aqueous humor of glaucomatous eyes. Sigma-1 receptor (S1R) has been shown to have neuroprotective effects in the retina, but data are lacking about its role in the TM. In this study, we identified the presence of S1R in mouse TM tissue and investigated the effect of an S1R agonist fluvoxamine (FLU) on TGFβ2-induced human TM cells regarding cell proliferation; ECM-related functions, including F-actin reorganization; and the accumulation of ECM elements. TGFβ2 increased the proliferation, cytoskeletal remodeling, and protein levels of fibronectin, collagen type IV, and connective tissue growth factor, and decreased the level of matrix metalloproteinase-2. Most importantly, FLU reversed all these effects of TGFβ2, suggesting that S1R agonists could be potential candidates for preserving TM function and thus maintaining normal IOP. |
| first_indexed | 2024-03-11T00:54:21Z |
| format | Article |
| id | doaj.art-f96803de5c6442e6ba0c523f26f6b606 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-11T00:54:21Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-f96803de5c6442e6ba0c523f26f6b6062023-11-18T20:10:33ZengMDPI AGLife2075-17292023-07-01137158110.3390/life13071581Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork CellsMinh Ngoc Tran0Timea Medveczki1Balazs Besztercei2Gyorgy Torok3Attila J. Szabo4Xavier Gasull5Illes Kovacs6Andrea Fekete7Judit Hodrea8MTA-SE Lendület “Momentum” Diabetes Research Group, Semmelweis University, 1083 Budapest, HungaryMTA-SE Lendület “Momentum” Diabetes Research Group, Semmelweis University, 1083 Budapest, HungaryInstitute of Clinical Experimental Research, Semmelweis University, 1094 Budapest, HungaryDepartment of Biophysics and Radiation Biology, Semmelweis University, 1094 Budapest, HungarySemmelweis University Pediatric Center, MTA Center of Excellence, 1083 Budapest, HungaryDepartment of Biomedicine, Institute of Neurosciences, University of Barcelona, 08035 Barcelona, SpainDepartment of Ophthalmology, Semmelweis University, 1085 Budapest, HungaryMTA-SE Lendület “Momentum” Diabetes Research Group, Semmelweis University, 1083 Budapest, HungaryMTA-SE Lendület “Momentum” Diabetes Research Group, Semmelweis University, 1083 Budapest, HungaryThe trabecular meshwork (TM) route is the principal outflow egress of the aqueous humor. Actin cytoskeletal remodeling in the TM and extracellular matrix (ECM) deposition increase TM stiffness, outflow resistance, and elevate intraocular pressure (IOP). These alterations are strongly linked to transforming growth factor-β2 (TGFβ2), a known profibrotic cytokine that is markedly elevated in the aqueous humor of glaucomatous eyes. Sigma-1 receptor (S1R) has been shown to have neuroprotective effects in the retina, but data are lacking about its role in the TM. In this study, we identified the presence of S1R in mouse TM tissue and investigated the effect of an S1R agonist fluvoxamine (FLU) on TGFβ2-induced human TM cells regarding cell proliferation; ECM-related functions, including F-actin reorganization; and the accumulation of ECM elements. TGFβ2 increased the proliferation, cytoskeletal remodeling, and protein levels of fibronectin, collagen type IV, and connective tissue growth factor, and decreased the level of matrix metalloproteinase-2. Most importantly, FLU reversed all these effects of TGFβ2, suggesting that S1R agonists could be potential candidates for preserving TM function and thus maintaining normal IOP.https://www.mdpi.com/2075-1729/13/7/1581Sigma-1 receptorfluvoxamineTGFβ2trabecular meshworkextracellular matrixcytoskeletal remodeling |
| spellingShingle | Minh Ngoc Tran Timea Medveczki Balazs Besztercei Gyorgy Torok Attila J. Szabo Xavier Gasull Illes Kovacs Andrea Fekete Judit Hodrea Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells Life Sigma-1 receptor fluvoxamine TGFβ2 trabecular meshwork extracellular matrix cytoskeletal remodeling |
| title | Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells |
| title_full | Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells |
| title_fullStr | Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells |
| title_full_unstemmed | Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells |
| title_short | Sigma-1 Receptor Activation Is Protective against TGFβ2-Induced Extracellular Matrix Changes in Human Trabecular Meshwork Cells |
| title_sort | sigma 1 receptor activation is protective against tgfβ2 induced extracellular matrix changes in human trabecular meshwork cells |
| topic | Sigma-1 receptor fluvoxamine TGFβ2 trabecular meshwork extracellular matrix cytoskeletal remodeling |
| url | https://www.mdpi.com/2075-1729/13/7/1581 |
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