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M. K. Call, H. Liu, Y. Hayashi, Y. Xia, W. W. Kao; Role of cJun in Corneal Wound Healing. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3405. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal wound healing involves a complex series of signaling events that ultimately modulate epithelial cell migration and proliferation for restoring corneal function. cJun, a major component of the activator protein-1 (AP-1) complex, is activated hours after wounding and appears essential for cell migration. This study is to determine the role of cJun at the early phase of healing following corneal epithelial debridement.
Adult AP-1-Luciferase transgenic mice were used to determine the activation of cJun following epithelium deridement. To ellucidate the role of cJun on wound healing, triple transgenic K12rtTA/rtTA/tet-O-Cre/cJunf/f mice were employed to ablate cJun in the corneal epithelium upon induction by doxycycline. Experimental mice were fed doxycylcine in the chow for 2 weeks and were then subjected to epithelial debridement using an Algerbrush II with a 2 mm burr. Un-induced mice were used as controls. Mice were sacrificied at 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, and 16 h following corneal wounding and corneas were collected and subjected to immunohistochemistry for components of various signaling pathways including TGF and Wnt in addition to proliferation and migration. Mice at the later time points, i.e., 12 h and 16 h, were injected with BrdU 2h prior to sacrifice to examine proiferation. All reported research was conducted in compliance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.
Luciferase activity was detected in AP-1 luciferase reporter mice at the leading edge of the injured cornea at 4 hours and decreased at 6 h post debridement, consistent with the up-regulation of cJun at the leading edge of migrating epithelium after debridement shown by immunohistochemistry with anti-cJun antibodies. During corneal wound healing p38 and Smad7 were upregulated 6-7 hours after wounding in wild type eyes. In the absence of cJun, beta-catenin expression at the leading edge of the wound was significantly reduced 1 h after wounding and remains so until approximately six hours, at which time beta-catenin expression resembled that of a wild type eye.
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