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Q. Li, Q. Lu, Y. Xin, F. Ye, G. Foulks; 14-3-3 Controls Corneal Epithelium Homeostasis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6370.
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To investigate the functional role of 14-3-3σ in regulation of the corneal epithelial proliferation, differentiation, and wound healing response.
The corneal phenotypes were investigated in repeated epilation (Er) mutant mice containing a mutation in sfn (14-3-3σ gene). The immunohistochemistry studies on cornea morphogenesis were performed on the embryonic day (E) 18.5 embryos of the 14-3-3σ homozygous mutated mice which completely lacking 14-3-3σ activity. We further investigated cornea homeostasis and wound healing response macroscopically and microscopically in adult Er heterozygous mice, which containing the reduced 14-3-3σ activity. The healing of corneal wounds after debridement were monitored and visualized by fluorenscin staining. Notch signaling activity was examined in the Er/+ corneal and mutant corneal epithelial cells with western analysis and Q-PCR method. Further functional connection between 14-3-3σ and Notch1 in corneal epithelial proliferation and differentiation was investigated in the primary corneal epithelial cells.
Homozygous mutation of 14-3-3σ led to defects in embryonic corneal epithelial development, whereas young heterozygotes showed normal corneal development and homeostasis. However, the aged heterozygotes displayed dramatic corneal plaque formation and wound healing defect. The phenotype of defective corneal epithelial wound repair and dysfunctional meibomian gland in Er/+ mice are similar to that seen with mutation of Notch1. More importantly, we demonstrated that mutation of 14-3-3σ led to loss of Notch1 expression. Expression of the active Notch1 rescues the block in mutant corneal epithelial cell differentiation.
14-3-3σ controls corneal epithelium proliferation and differentiation, and plays an important role in the corneal epithelium development and daily renewing of adult corneal epithelium. 14-3-3σ regulates cornea epithelial homeostasis and wound healing through Notch signaling activity.
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