| First Author | Korol A | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 7 | Pages | 2001-12 |
| PubMed ID | 24814605 | Mgi Jnum | J:211036 |
| Mgi Id | MGI:5573059 | Doi | 10.1016/j.ajpath.2014.03.013 |
| Citation | Korol A, et al. (2014) Matrix Metalloproteinase-9-Null Mice Are Resistant to TGF-beta-Induced Anterior Subcapsular Cataract Formation. Am J Pathol 184(7):2001-12 |
| abstractText | Epithelial-mesenchymal transition (EMT) is associated with fibrotic diseases in the lens, such as anterior subcapsular cataract (ASC) formation. Often mediated by transforming growth factor (TGF)-beta, EMT in the lens involves the transformation of lens epithelial cells into a multilayering of myofibroblasts, which manifest as plaques beneath the lens capsule. TGF-beta-induced EMT and ASC have been associated with the up-regulation of two matrix metalloproteinases (MMPs): MMP-2 and MMP-9. The current study used MMP-2 and MMP-9 knockout (KO) mice to further determine their unique roles in TGF-beta-induced ASC formation. Adenoviral injection of active TGF-beta1 into the anterior chamber of all wild-type and MMP-2 KO mice led to the formation of distinct ASC plaques that were positive for alpha-smooth muscle actin, a marker of EMT. In contrast, only a small proportion of the MMP-9 KO eyes injected with adenovirus-expressing TGF-beta1 exhibited ASC plaques. Isolated lens epithelial explants from wild-type and MMP-2 KO mice that were treated with TGF-beta exhibited features indicative of EMT, whereas those from MMP-9 KO mice did not acquire a mesenchymal phenotype. MMP-9 KO mice were further bred onto a TGF-beta1 transgenic mouse line that exhibits severe ASC formation, but shows a resistance to ASC formation in the absence of MMP-9. These findings suggest that MMP-9 expression is more critical than MMP-2 in mediating TGF-beta-induced ASC formation. |
