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BMP and Activin Membrane Bound Inhibitor Regulates the Extracellular Matrix in the Trabecular Meshwork

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Τίτλος: BMP and Activin Membrane Bound Inhibitor Regulates the Extracellular Matrix in the Trabecular Meshwork
Συγγραφείς: Hernandez, Humberto, Millar, J. Cameron, Curry, Stacy M., Clark, Abbot F., McDowell, Colleen M.
Πηγή: Investigative Ophthalmology & Visual Science
Στοιχεία εκδότη: ARVO Journals
Έτος έκδοσης: 2022
Συλλογή: UNTHSC Scholarly Repository (University. of North Texas Health Science Center)
Θεματικοί όροι: 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
Περιγραφή: 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).
Τύπος εγγράφου: article in journal/newspaper
Περιγραφή αρχείου: application/pdf
Γλώσσα: unknown
Relation: https://doi.org/10.1167/iovs.17-23282; https://hdl.handle.net/20.500.12503/31721; 59
Διαθεσιμότητα: https://hdl.handle.net/20.500.12503/31721
Rights: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; Copyright 2018 The Authors
Αριθμός Καταχώρησης: edsbas.7B2FE1A7
Βάση Δεδομένων: BASE
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  Data: BMP and Activin Membrane Bound Inhibitor Regulates the Extracellular Matrix in the Trabecular Meshwork
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  Data: <searchLink fieldCode="AR" term="%22Hernandez%2C+Humberto%22">Hernandez, Humberto</searchLink><br /><searchLink fieldCode="AR" term="%22Millar%2C+J%2E+Cameron%22">Millar, J. Cameron</searchLink><br /><searchLink fieldCode="AR" term="%22Curry%2C+Stacy+M%2E%22">Curry, Stacy M.</searchLink><br /><searchLink fieldCode="AR" term="%22Clark%2C+Abbot+F%2E%22">Clark, Abbot F.</searchLink><br /><searchLink fieldCode="AR" term="%22McDowell%2C+Colleen+M%2E%22">McDowell, Colleen M.</searchLink>
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  Data: Investigative Ophthalmology & Visual Science
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  Data: 2022
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  Data: UNTHSC Scholarly Repository (University. of North Texas Health Science Center)
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  Data: <searchLink fieldCode="DE" term="%22Adenoviridae+%2F+genetics%22">Adenoviridae / genetics</searchLink><br /><searchLink fieldCode="DE" term="%22Animals%22">Animals</searchLink><br /><searchLink fieldCode="DE" term="%22Bone+Morphogenetic+Proteins+%2F+physiology%22">Bone Morphogenetic Proteins / physiology</searchLink><br /><searchLink fieldCode="DE" term="%22Cells%22">Cells</searchLink><br /><searchLink fieldCode="DE" term="%22Cultured%22">Cultured</searchLink><br /><searchLink fieldCode="DE" term="%22Dexamethasone+%2F+pharmacology%22">Dexamethasone / pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22Extracellular+Matrix+Proteins+%2F+metabolism%22">Extracellular Matrix Proteins / metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Glucocorticoids+%2F+pharmacology%22">Glucocorticoids / pharmacology</searchLink><br /><searchLink fieldCode="DE" term="%22Intraocular+Pressure+%2F+physiology%22">Intraocular Pressure / physiology</searchLink><br /><searchLink fieldCode="DE" term="%22Membrane+Proteins+%2F+physiology%22">Membrane Proteins / physiology</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Inbred+C57BL%22">Inbred C57BL</searchLink><br /><searchLink fieldCode="DE" term="%22Knockout%22">Knockout</searchLink><br /><searchLink fieldCode="DE" term="%22Ocular+Hypertension+%2F+metabolism%22">Ocular Hypertension / metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Trabecular+Meshwork+%2F+metabolism%22">Trabecular Meshwork / metabolism</searchLink><br /><searchLink fieldCode="DE" term="%22Transfection%22">Transfection</searchLink><br /><searchLink fieldCode="DE" term="%22Transforming+Growth+Factor+beta2+%2F+pharmacology%22">Transforming Growth Factor beta2 / pharmacology</searchLink>
– Name: Abstract
  Label: Description
  Group: Ab
  Data: 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).
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  Data: https://doi.org/10.1167/iovs.17-23282; https://hdl.handle.net/20.500.12503/31721; 59
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  Data: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ; http://creativecommons.org/licenses/by-nc-nd/4.0/ ; Copyright 2018 The Authors
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      – Text: unknown
    Subjects:
      – SubjectFull: Adenoviridae / genetics
        Type: general
      – SubjectFull: Animals
        Type: general
      – SubjectFull: Bone Morphogenetic Proteins / physiology
        Type: general
      – SubjectFull: Cells
        Type: general
      – SubjectFull: Cultured
        Type: general
      – SubjectFull: Dexamethasone / pharmacology
        Type: general
      – SubjectFull: Extracellular Matrix Proteins / metabolism
        Type: general
      – SubjectFull: Glucocorticoids / pharmacology
        Type: general
      – SubjectFull: Intraocular Pressure / physiology
        Type: general
      – SubjectFull: Membrane Proteins / physiology
        Type: general
      – SubjectFull: Mice
        Type: general
      – SubjectFull: Inbred C57BL
        Type: general
      – SubjectFull: Knockout
        Type: general
      – SubjectFull: Ocular Hypertension / metabolism
        Type: general
      – SubjectFull: Trabecular Meshwork / metabolism
        Type: general
      – SubjectFull: Transfection
        Type: general
      – SubjectFull: Transforming Growth Factor beta2 / pharmacology
        Type: general
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      – TitleFull: BMP and Activin Membrane Bound Inhibitor Regulates the Extracellular Matrix in the Trabecular Meshwork
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            NameFull: Hernandez, Humberto
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            NameFull: Millar, J. Cameron
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              Y: 2022
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            – TitleFull: Investigative Ophthalmology & Visual Science
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