دورية أكاديمية
BMP and Activin Membrane Bound Inhibitor Regulates the Extracellular Matrix in the Trabecular Meshwork
| العنوان: | BMP and Activin Membrane Bound Inhibitor Regulates the Extracellular Matrix in the Trabecular Meshwork |
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| المؤلفون: | Hernandez, Humberto, Millar, J. Cameron, Curry, Stacy M., Clark, Abbot F., McDowell, Colleen M. |
| المصدر: | Investigative Ophthalmology & Visual Science |
| بيانات النشر: | ARVO Journals |
| سنة النشر: | 2022 |
| المجموعة: | UNTHSC Scholarly Repository (University. of North Texas Health Science Center) |
| مصطلحات موضوعية: | Adenoviridae / genetics, Animals, Bone Morphogenetic Proteins / physiology, Cells, Cultured, Dexamethasone / pharmacology, Extracellular Matrix Proteins / metabolism, Glucocorticoids / pharmacology, Intraocular Pressure / physiology, Membrane Proteins / physiology, Mice, Inbred C57BL, Knockout, Ocular Hypertension / metabolism, Trabecular Meshwork / metabolism, Transfection, Transforming Growth Factor beta2 / pharmacology |
| الوصف: | Purpose: The trabecular meshwork (TM) has an important role in the regulation of aqueous humor outflow and IOP. Regulation of the extracellular matrix (ECM) by TGFbeta2 has been studied extensively. Bone morphogenetic protein (BMP) and activin membrane-bound inhibitor (BAMBI) has been shown to inhibit or modulate TGFbeta2 signaling. We investigate the role of TGFbeta2 and BAMBI in the regulation of TM ECM and ocular hypertension. Methods: Mouse TM (MTM) cells were isolated from B6;129S1-Bambitm1Jian/J flox mice, characterized for TGFbeta2 and dexamethasone (DEX)-induced expression of fibronectin, collagen-1, collagen-4, laminin, alpha-smooth muscle actin, cross-linked actin networks (CLANs) formation, and DEX-induced myocilin (MYOC) expression. MTM cells were transduced with Ad5.GFP to identify transduction efficiency. MTM cells and mouse eyes were transduced with Ad5.Null, Ad5.Cre, Ad5.TGFbeta2, or Ad5.TGFbeta2 + Ad5.Cre to evaluate the effect on ECM production, IOP, and outflow facility. Results: MTM cells express TM markers and respond to DEX and TGFbeta2. Ad5.GFP at 100 MOI had the highest transduction efficiency. Bambi knockdown by Ad5.Cre and Ad5.TGFbeta2 increased fibronectin, collagen-1, and collagen-4 in TM cells in culture and tissue. Ad5.Cre, Ad5.TGFbeta2, and Ad5.TGFbeta2 + Ad5.Cre each significantly induced ocular hypertension and lowered aqueous humor outflow facility in transduced eyes. Conclusions: We show for the first time to our knowledge that knockdown of Bambi alters ECM expression in cultured cells and mouse TM, reduces outflow facility, and causes ocular hypertension. These data provide a novel insight into the development of glaucomatous TM damage and identify BAMBI as an important regulator of TM ECM and ocular hypertension. ; Supported by the Bright Focus Foundation G2014063 (CMM), National Institutes of Health R01EY026529 (CMM), and Neurobiology of Aging Training Grant T32AG020494 (HH). |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 1552-5783 |
| العلاقة: | https://doi.org/10.1167/iovs.17-23282Test; Hernandez, H., Millar, J. C., Curry, S. M., Clark, A. F., & McDowell, C. M. (2018). BMP and Activin Membrane Bound Inhibitor Regulates the Extracellular Matrix in the Trabecular Meshwork. Investigative ophthalmology & visual science, 59(5), 2154-2166. https://doi.org/10.1167/iovs.17-23282Test; https://hdl.handle.net/20.500.12503/31721Test; 59 |
| الإتاحة: | https://doi.org/20.500.12503/31721Test https://doi.org/10.1167/iovs.17-23282Test https://hdl.handle.net/20.500.12503/31721Test |
| حقوق: | Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ; http://creativecommons.org/licenses/by-nc-nd/4.0Test/ ; Copyright 2018 The Authors |
| رقم الانضمام: | edsbas.7B2FE1A7 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15525783 |
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