Keratinocyte growth factor (KGF) induces stem/progenitor cell growth in middle ear mucosa.

OBJECTIVE: The middle ear epithelium is derived from the neural crest and endoderm, which line distinct regions of the middle ear cavity. In this study, we investigated the localization of stem/progenitor cells in the middle ear mucosa of adult mice and the effects of keratinocyte growth factor (KGF) on the cell kinetics of stem/progenitor cells in vivo. METHODS: In this study, after KGF-expression vector was transfected in the ear, two kinds of thymidine analogues, BrdU and EdU, were transferred at different time points. BrdU was detected by immunohistochemistry and EdU was detected by click chemistry. We also performed immunohistochemistry using anti-Keratin14 (K14) antibody (an undifferentiated epithelial cell marker), anti-p63 antibody (a stem/progenitor cell marker) and anti-acetylated α-tubulin antibody (a ciliated epithelial cell marker). RESULTS: A large number of EdU-positive cells were detected in the thickened mucosal epithelium of the pars flaccida and attic region at Day 1 after KGF transfection. Interestingly, in the mucosal epithelium overlying the promontory of the cochlea, many EdU-positive cells were detected. These cells were also positive for K14 and p63. The acetylated α-tubulin positive cells were reduced in the attic region at Day 1 after KGF transfection. CONCLUSION: These findings indicate that KGF over-expression may increase stem/progenitor cell proliferation in the mucosal epithelium not only within the attic which is typical in middle ear cholesteatoma, but also overlying the promontory of the cochlea.