| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Department of Pathology and Molecular Medicine* and the Division of Nephrology, McMaster University, Hamilton; and the School of Optometry, University of Waterloo, Waterloo, Ontario, Canada
The pleotropic morphogen transforming growth factor-ß (TGFß) plays an important role in the development of fibrotic pathologies, including anterior subcapsular cataracts (ASCs). ASC formation involves increased proliferation and transition of lens epithelial cells into myofibroblasts, through epithelial-mesenchymal transformation that results in opaque plaques beneath the lens capsule. In this study, we used a previously established TGFß-induced rat cataract model to explore the role of matrix metalloproteinases (MMPs) in ASC formation. Treatment of excised rat lenses with TGFß resulted in enhanced secretion of MMP-2 and MMP-9. Importantly, co-treatment with two different MMP inhibitors (MMPIs), the broad spectrum inhibitor GM6001 and an MMP-2/9-specific inhibitor, suppressed TGFß-induced ASC changes, including the epithelial-mesenchymal transformation of lens epithelial cells. Using an anti-E-cadherin antibody, we revealed that conditioned media from lenses treated with TGFß contained a 72-kd E-cadherin fragment, indicative of E-cadherin shedding. This was accompanied by attenuated levels of E-cadherin mRNA. Conditioned media from lenses co-treated with TGFß and MMPIs exhibited attenuated levels of the E-cadherin fragment compared with those from TGFß-treated lenses. Together, these findings demonstrate that TGFß-induced E-cadherin shedding in the lens is mediated by MMPs and that suppression of this phenomenon might explain the mechanism by which MMPIs inhibit ASC plaque formation.
This article has been cited by other articles:
 |
|
 |
|
  M.-C. Lauzier, G. A. Robitaille, D. A. Chan, A. J. Giaccia, and D. E. Richard (2R)-[(4-Biphenylylsulfonyl)amino]-N-hydroxy-3-phenylpropionamide (BiPS), a Matrix Metalloprotease Inhibitor, Is a Novel and Potent Activator of Hypoxia-Inducible Factors Mol. Pharmacol., July 1, 2008; 74(1): 282 - 288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Cowden Dahl, J. Symowicz, Y. Ning, E. Gutierrez, D. A. Fishman, B. P. Adley, M. S. Stack, and L. G. Hudson Matrix Metalloproteinase 9 Is a Mediator of Epidermal Growth Factor-Dependent E-Cadherin Loss in Ovarian Carcinoma Cells Cancer Res., June 15, 2008; 68(12): 4606 - 4613. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Cao, C. Chiarelli, O. Richman, K. Zarrabi, P. Kozarekar, and S. Zucker Membrane Type 1 Matrix Metalloproteinase Induces Epithelial-to-Mesenchymal Transition in Prostate Cancer J. Biol. Chem., March 7, 2008; 283(10): 6232 - 6240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M.D. Tholozan, C. Gribbon, Z. Li, M. W. Goldberg, A. R. Prescott, N. McKie, and R. A. Quinlan FGF-2 Release from the Lens Capsule by MMP-2 Maintains Lens Epithelial Cell Viability Mol. Biol. Cell, November 1, 2007; 18(11): 4222 - 4231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Hodgkinson, G. Duncan, L. Wang, C. J. Pennington, D. R. Edwards, and I. M. Wormstone MMP and TIMP Expression in Quiescent, Dividing, and Differentiating Human Lens Cells Invest. Ophthalmol. Vis. Sci., September 1, 2007; 48(9): 4192 - 4199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Symowicz, B. P. Adley, K. J. Gleason, J. J. Johnson, S. Ghosh, D. A. Fishman, L. G. Hudson, and M. S. Stack Engagement of Collagen-Binding Integrins Promotes Matrix Metalloproteinase-9-Dependent E-Cadherin Ectodomain Shedding in Ovarian Carcinoma Cells Cancer Res., March 1, 2007; 67(5): 2030 - 2039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Banh, P. A. Deschamps, J. Gauldie, P. A. Overbeek, J. G. Sivak, and J. A. West-Mays Lens-Specific Expression of TGF-{beta} Induces Anterior Subcapsular Cataract Formation in the Absence of Smad3. Invest. Ophthalmol. Vis. Sci., August 1, 2006; 47(8): 3450 - 3460. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
