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Jie Wang, Andrew Lin, Luo Lu; Effect of EGF-Induced HDAC6 Activation on Corneal Epithelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 2010;51(6):2943-2948. doi: https://doi.org/10.1167/iovs.09-4639.
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© ARVO (1962-2015); The Authors (2016-present)
Epidermal growth factor (EGF) stimulates migration in corneal epithelial wound healing. The purpose of this study was to investigate the effect of EGF-induced α-tubulin deacetylation through activating HDAC6 on migration in corneal epithelial wound healing.
Human corneal epithelial (HCE) cells were cultured in DMEM/F12 medium containing 10% FBS in a 37°C incubator supplied with 5% CO2. Western blot analysis was used to determine protein expression. Activity of HDAC6 was suppressed by trichostatin A (TSA) and by siRNA specific to HDAC6. Corneal epithelial cell migration was measured by using scratch-induced directional migration assay in cultured cells and by corneal epithelial debridement using a mouse whole-eye organ culture model.
The authors found EGF stimulated corneal epithelial cell migration in wound healing by enhancing HDAC6 activity, resulting in the deacetylation of α-tubulin. EGF stimulated HDAC6 enzymatic activity and protein translocation toward the leading edge of the cell. Inhibition of HDAC6 activity by TSA significantly suppressed EGF-induced cell migration and delayed EGF-induced wound healing in epithelially debrided mouse corneas. In the meantime, knockdown of HDAC6 mRNA with specific siRNA effectively abolished EGF-induced deacetylation of α-tubulin, resulting in the inhibition of cell migration.
These results reveal an important mechanism that involves EGF-induced HDAC6 activation and α-tubulin deacetylation, subsequently affecting corneal epithelial migration in the wound-healing process.
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