STAT3 Regulates the Proliferation and Differentiation of Rabbit Limbal Epithelial Cells via a ΔNp63-Dependent Mechanism

PURPOSE. To explore the roles of STAT3 in the regulation of Delta Np63-dependent proliferation and differentiation of rabbit limbal keratinocytes. METHODS. siRNAs were designed to specifically suppress the expression of STAT3 and Delta Np63, and their effects on limbal epithelial cell proliferation and differentiation were examined. Ectopically expressed Delta Np63 was used to compensate for the decreased endogenous Delta Np63. Immunoblot was used to examine the expressions of STAT3, Delta Np63, K3, integrin beta 1, and involucrin. RESULTS. Limbal tissue expresses higher level of phosphorylated and nuclear translocated STAT3 compared with that of the cornea. Knockdown of STAT3 expression reduces the expression of Delta Np63, inhibits the expansion of limbal epithelial outgrowth, suppresses the expression of integrin beta 1, and promotes the expression of involucrin. CONCLUSIONS. STAT3 enhances the proliferation of limbal keratinocytes through a Delta Np63-dependent mechanism. Suppression of this pathway inhibits cell proliferation with a concomitant increase of cell differentiation. (Invest Ophthalmol Vis Sci. 2011;52:4685-4693) DOI:10.1167/iovs.10-6103