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C. Sun, C. Yang; Low Dose Ultraviolet Irradiation Induces Proliferation of Corneal Epithelial Cells via Activation of p42/p44 MAPK Pathway . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1375.
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Purpose: To elucidate the signaling pathways involved in the ultraviolet B (UVB) irradiation-induced mitogenic response on cultured corneal epithelial cells. Methods: Cultured rabbit corneal epithelial cells were exposed to a single dose of UVB irradiation (300 J/m2). Cells pretreated with specific MEK1/2 inhibitor, U0126, or not were assayed for proliferation with [3H]-thymidine incorporation. Whole cell, cytoplasmic and nuclear p42/p44 mitogen-activated protein kinase (MAPK) as well as nuclear c-Fos and c-Jun protein expression were determined using Western blot analysis. Nuclear translocation of cytoplasmic MAPK was detected using an immunofluorescence microscopy. Results: Exposure of cultured rabbit corneal epithelial cells to a single dose UVB irradiation induced a maximal cell proliferation within 48 h. Western blot analysis for whole cell and nuclear p42/p44 MAPK demonstrated biphasic elevation of their activity, with two peaks at 15 min and 4 h after UVB irradiation. Nuclear c-Fos and c-Jun, together as nuclear transcription factor activating protein 1 (AP-1) were known to be associated with cell survival, proliferation and differentiation. In our study, AP-1 was also activated 15 min and 16 h after exposure of UVB irradiation. U0126, a specific MEK1/2 inhibitor, not only blocked the short term activity of p42/p44 MAPK expression, but also inhibited UVB-induced DNA proliferation measured by [3H]-thymidine incorporation. Most of p42/p44 MAPK distributed in cytoplasm at resting state of corneal epithelial cells. While p42/p44 MAPK translocated from cytoplasm into nucleus 16 h after irradiation of these cells, revealed by an immunofluorescence microscopy. Conclusions: Low dose UVB irradiation induces corneal epithelial cell proliferation, which may implicate in many ocular surface diseases. This cell proliferation may be associated with the activation of p42/p44 MAPK and subsequentially potentiate the expression of transcription factors such as AP-1 in corneal epithelial cells.
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