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

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/EBPδ 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.

Enterotoxin‐related genes PPFIA4 and SCN3B promote colorectal cancer development and progression

“…Similarly, MLN4924 was reported to promote self‐renewal of limbal stem cells and ocular surface restoration. [ 45 ] Meanwhile, it can inhibit both the tumor stroma and angiogenesis in pancreatic cancer via Gli1 and REDD1 related pathways. [ 46 ] Moreover, MLN4924 was found to inhibit cell proliferation by targeting the activated neddylation pathway in endometrial carcinoma.…”

Advancements in Ocular Regenerative Therapies

“…An example of such an indirect approach representing recent discoveries suggests topical supplementation with substances that would stimulate corneal regeneration. This concept has been advanced by Li Q et al; while still in the animal models, supplementation of MLN4924 resulted in faster corneal regeneration by remnant LSCs [66]. Alternatively, a discovery by Jang et al offers an entirely different approach with potentially the same effect [67].…”