Role of the C-Jun N-Terminal Kinase (JNK) in the Corneal Epithelial Wound Healing

Abstract

Abstract: : Purpose:We previously demonstrated that AP-1 is transiently up-regulated in healing corneal epithelium following epithelial debridement. In response to stress stimuli or cytokine exposure, dual Thr- and Tyr-phosphorylations of c-Jun N-terminal kinase (JNK) result in its activation and in further activation of transcription factors including c-Jun. Here we examined the role of JNK in corneal epithelial wound healing. Methods: 1) A central epithelial defect in one cornea of C57BL/6 mice (n=19) were allowed to heal. Animals were killed and the frozen sections of the affected eye were immunostained with an anti-phospho-JNK antibody. 2) Mouse eye globes with a central corneal epithelial defect (n=26) were incubated for 6 - 48h in culture medium with or without a JNK inhibitor (5.0 mM) and closure of the defect was evaluated. 3) Corneal blocks (2x4mm) obtained from a rabbit cornea were incubated for 24h with or without the inhibitor. Epithelial spreading on stromal cut surface was histologically measured. Results:1) No or very faint immunoreaction for JNK was detected in uninjured epithelium. Three to 24h after the treatment, phospho-JNK immunoreactivity was detected in the epithelium surrounding the defect of mouse corneas. 2) Adding a JNK inhibitor to the medium retarded the closure of the defect approximately 35% less than control at both 18 and 24 hr cultures in mouse corneas (p<0.05). 3) In culture of rabbit corenal blocks, addition of the JNK inhibitor decreased epithelial spreading to around 65% of control (p<0.01). Conclusions:Signaling cascade involving phosphorylated JNK may have an important role in epithelial cell migration during wound healing.

Keywords: wound healing • cornea: epithelium • transcription factors