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Inhibition of matrix metalloproteinase activity reverses corneal endothelial-mesenchymal transition.

Publication ,  Journal Article
Ho, W-T; Chang, J-S; Su, C-C; Chang, S-W; Hu, F-R; Jou, T-S; Wang, I-J
Published in: Am J Pathol
August 2015

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 β-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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Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

August 2015

Volume

185

Issue

8

Start / End Page

2158 / 2167

Location

United States

Related Subject Headings

  • Wnt Signaling Pathway
  • Up-Regulation
  • Transcription Factors
  • Snail Family Transcription Factors
  • Rats, Sprague-Dawley
  • Rats
  • Phosphorylation
  • Pathology
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase Inhibitors
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ho, W.-T., Chang, J.-S., Su, C.-C., Chang, S.-W., Hu, F.-R., Jou, T.-S., & Wang, I.-J. (2015). Inhibition of matrix metalloproteinase activity reverses corneal endothelial-mesenchymal transition. Am J Pathol, 185(8), 2158–2167. https://doi.org/10.1016/j.ajpath.2015.04.005
Ho, Wei-Ting, Jung-Shen Chang, Chien-Chia Su, Shu-Wen Chang, Fung-Rong Hu, Tzuu-Shuh Jou, and I-Jong Wang. “Inhibition of matrix metalloproteinase activity reverses corneal endothelial-mesenchymal transition.Am J Pathol 185, no. 8 (August 2015): 2158–67. https://doi.org/10.1016/j.ajpath.2015.04.005.
Ho W-T, Chang J-S, Su C-C, Chang S-W, Hu F-R, Jou T-S, et al. Inhibition of matrix metalloproteinase activity reverses corneal endothelial-mesenchymal transition. Am J Pathol. 2015 Aug;185(8):2158–67.
Ho, Wei-Ting, et al. “Inhibition of matrix metalloproteinase activity reverses corneal endothelial-mesenchymal transition.Am J Pathol, vol. 185, no. 8, Aug. 2015, pp. 2158–67. Pubmed, doi:10.1016/j.ajpath.2015.04.005.
Ho W-T, Chang J-S, Su C-C, Chang S-W, Hu F-R, Jou T-S, Wang I-J. Inhibition of matrix metalloproteinase activity reverses corneal endothelial-mesenchymal transition. Am J Pathol. 2015 Aug;185(8):2158–2167.
Journal cover image

Published In

Am J Pathol

DOI

EISSN

1525-2191

Publication Date

August 2015

Volume

185

Issue

8

Start / End Page

2158 / 2167

Location

United States

Related Subject Headings

  • Wnt Signaling Pathway
  • Up-Regulation
  • Transcription Factors
  • Snail Family Transcription Factors
  • Rats, Sprague-Dawley
  • Rats
  • Phosphorylation
  • Pathology
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase Inhibitors