MLN4924 Promotes Self-Renewal of Limbal Stem Cells and Ocular Surface Restoration

Q.J. Li, Y.K. Shen, S.A. Wu, H. Wei, J. Zou, S.H. Xu, Q. Ling, M. Kang, H. Huang, X. Chen, Y. Shao*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Objective: To study the role of MLN4924 in corneal stem cell maintenance and corneal injury repair. Methods: In cell experiments, the Sprague-Dawley (SD) rat corneal epithelial cells were co-cultured with mitomycin C-inactivated mouse feeder cells in a supplemental hormonal epithelial medium (SHEM) with or without MLN4924. Cells were photographed using an optical microscope. Furthermore, we performed crystal violet, polymerase chain reaction (PCR), and immunofluorescence staining on limbal stem cells (LSCs). In animal experiments, we scraped the corneal epithelium with a central corneal diameter of 4 mm in SD rats. The area of the corneal epithelial defect was calculated by fluorescein sodium staining. Results: LSCs in the MLN4924 group had significantly proliferated. The MLN4924 treatment evidently enhanced the clone formation rate and clone area of LSCs. The expression levels of Ki67, p63, ABCG2, Bmi1, and C/EBP delta increased in LSCs after MLN4924 treatment, whereas the expression of K12 decreased. At 12 and 24 h after scraping, the corneal epithelium recovery rate in the eyes of the MLN4924-treated rats was accelerated. Conclusions: MLN4924 can maintain stemness, reduce differentiation, promote the proliferative capacity of rat LSCs, and accelerate corneal epithelial wound healing in SD rats.
Original languageEnglish
Article number379
Number of pages14
JournalJournal of Personalized Medicine
Volume13
Issue number3
DOIs
Publication statusPublished - 1 Mar 2023

Keywords

  • limbal stem cells
  • MLN4924
  • proliferation
  • differentiation
  • wound healing
  • CULLIN-RING LIGASES
  • NEDD8-ACTIVATING ENZYME
  • NEDDYLATION
  • PROLIFERATION
  • INHIBITOR
  • P63
  • PEVONEDISTAT
  • MAINTENANCE
  • EPITHELIUM
  • APOPTOSIS

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