Inhibition of matrix metalloproteinase activity reverses corneal endothelial-mesenchymal transition.
Am J Pathol
; 185(8): 2158-67, 2015 Aug.
Article
em En
| MEDLINE
| ID: mdl-26216284
ABSTRACT
Ex vivo culture or regeneration of corneal endothelial cells often is subjected to gradual endothelial-mesenchymal transition and loss of function. Here, we found that during ex vivo culture, bovine corneal endothelial cells underwent endothelial-mesenchymal transition and had an up-regulated expression and activity of matrix metalloproteinases. Inhibition of matrix metalloproteinase activity in confluent bovine corneal endothelial cells decreased the level of endothelial-mesenchymal transition regulators snail and slug. The phosphorylation and degradation of the key Wnt signaling pathway modulator active ß-catenin also were accelerated with the broad-spectrum matrix metalloproteinase inhibitor Marimastat, which may result from decreased N-cadherin shedding and increased intact N-cadherin molecules on the cell membrane. Intracameral injection of Marimastat also suppressed basic fibroblast growth factor-induced endothelial-mesenchymal transition in a rat corneal endothelium cryo-injury model and significantly diminished the corneal edema. Our study indicated that inhibition of matrix metalloproteinase activity can reverse endothelial-mesenchymal transition and preserve the function of corneal endothelial cells both during ex vivo culture and in vivo. This may offer a potential therapeutic target in regenerative medicine for the treatment of corneal endothelial dysfunctions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Endotélio Corneano
/
Metaloproteinases da Matriz
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article