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Y. Okada, S. Saika, K. Shirai, O. Yamanaka, Y. Ohnishi, P.S. Reinach; Epidermal Growth Factor Induces C–Fos Expression and Wound Closure in Human Corneal Epithelial Cell Line . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5044.
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To identify the upstream mediators that affect prolonged activation of c–fos in response to EGF during wound healing in a human corneal epithelial cell line (HCE), we applied different siganling inhibitors to the HCE cell culture. We previously demonstrated that AP–1 components, c–fos/c–jun, are up–regulated in healing rat corneal epithelium in relatively early phase following epithelial debridement.
A linear epithelial defect was produced in a HCE monolayer. Healing kinetics were evaluated in presence and absence of the following selective inhibitors: 1) JNK inhibitor 1, (JNK); 2) SB203580, (p38); 3) UO126, (Erk1/2); 4) AG1478, (EGF receptor); 5) U71322 (PLC) 6) LY294002 (PI–3 kinase) with or without EGF (10ng/ml). Moreover, these HCE monolayers were immunohistochemically stained with c–Fos antibody.
EGF promoted wound closure and up–regulated c–Fos protein expression. Each inhibitor decreased defect healing in HCE culture. Inhibition of p38 MAPK signaling suppressed healing more than any of the aforementioned other inhibitors. The rank order of inhibition was: p38 > JNK > EGF receptor > Erk1/2 > PI–3 kinase > PLC. Only Erk1/2 inhibitor suppressed c–Fos protein expression.
Blocking Erk1/2 activation by treatment with U0126 suppressed wound closure and c–Fos protein expression. MAP kinase/Erk–deriven c–Fos/AP–1 signal might have a critical role in corneal epithelial wound healing
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