期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 185, 期 8, 页码 2158-2167出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2015.04.005
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资金
- Ministry of Health [DOH100-TD-PB-111-TM005, DOH101-TD-PB-111-TM017, DOH102-TD-PB-111-TM013]
- Ministry of Science and Technology [100-2314-B-002-061-MY3, 102-2314-B-002-112-MY3]
- National Taiwan University Hospital grants [102-CGN01, 103-S2463]
- Far Eastern Memorial Hospital grant [FEMH-2015-D-052]
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 beta-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.
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