Date of Award

5-1-2008

Degree Type

Restricted Access Dissertation

Degree Name

Doctor of Philosophy

Department

Graduate School of Biomedical Sciences

First Advisor

Dan S. Dimitrijevich

Second Advisor

Porunelloor Mathew

Third Advisor

Julian Borejdo

Abstract

Epithelial differentiation is a highly coordinated process that is essential for proper function of epithelia in their respective tissues. In the cornea epithelial differentiation is necessary to maintain transparency of the cornea, which is essential for vision. 14-3-3σ/stratifin is a proposed epithelial cell marker, which is up regulated in response to UV damage. This up-regulation causes the cells to arrest in G2/M phase so that DNA repair can take place. In a number of epithelial cancers 14-3-3σ has been shown to be down-regulated. The function of 14-3-3σ in the corneal epithelium and other stratified epithelial tissues other than the skin has not been studied. In the cornea are no reports of hyperplasia so it would be a good model to study the role of this protein. In this study, for the first time we have evaluated the expression of 14-3-3 family of proteins in the cornea. We have also shown the involvement of 14-3-3σ in the process of corneal epithelial differentiation in vitro using primary corneal epithelial cells and in vivo using the Er/+ mouse model. We have also been able to extend in vitro lifespan of corneal epithelial cells by down regulating 14-3-3σ expression. The down regulation also resulted in immortalization and generation of a corneal epithelial cell line. We have characterized and shown that this cell line is a suitable model to study signaling cascades involving corneal epithelial proliferation, differentiation and apoptosis. Preliminary data presented in this study also imply that ΔNp63 is an upstream regulator of 14-3-3σ expression.

Comments

W 4 S528R 2008

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