Chitosan Promoted the Corneal Epithelial Wound Healing via Activation of ERK Pathway

Abstract

ABSTRACTPurpose: To investigate the mechanism of chitosan promoting corneal wound healing though evaluating its effect on extracellular signal-regulated kinases (ERK) and p38 pathway activity in a rabbit animal model.Methods: Cell proliferation and migration assay were performed 24 hours after chitosan treatment. The activity of ERK and p38 pathways was detected by using immunofluorescence and Western blotting in the presence of chitosan and an ERK inhibitor. In vivo study of epithelial debridement wounds was performed on 8 mm rabbit corneas in the presence of chitosan and an ERK pathway inhibitor.Results: Immunostaining with Ki67 and migrating assay showed that chitosan could upregulate the cell proliferation and promote the cell migration. Chitosan activated the ERK pathway in 5 min to 30 min after treatment but did not affect the p38 pathway. ERK inhibitor PD98059 can inhibit the chitosan-stimulated ERK phosphorylation. Chitosan increased the corneal epithelial wound closure in organ culture and ERK inhibition with PD98059 blocked the effect of chitosan on wound healing.Conclusions: Chitosan promoted corneal epithelial proliferation and migration during the wound healing in rabbits’ eye. Chitosan-stimulated epithelial wound healing is partially mediated through the activation of the ERK pathway but not the p38 pathway.