Netrins are secreted
chemoattractants with the roles in axon guidance, cell migration and epithelial plasticity. In the present study, we investigated the roles of
netrin-1 in the regulation of corneal epithelial wound healing,
inflammation response and nerve fiber regeneration in diabetic mice and cultured corneal epithelial cells. In diabetic mice, the expression of
netrin-1 was decreased when compared with that of normal mice. Furthermore, high
glucose blocked the wounding-induced up-regulation of
netrin-1 expression in corneal epithelial cells. Exogenous
netrin-1 promoted the corneal epithelial wound healing in diabetic mice, and facilitated the proliferation and migration by reactivating the phosphorylation of ERK and EGFR in high-
glucose treated corneal epithelial cells. Moreover,
netrin-1 decreased the neutrophil infiltration and promoted M2 macrophage transition, accompanied with the attenuated expression of pro-inflammatory factors in diabetic mouse corneal epithelium. The promotions of
netrin-1 on corneal epithelial wound healing and
inflammation resolution were mediated at least through the
adenosine 2B receptor. In addition,
netrin-1 promoted the regeneration of corneal nerve fibers that was impaired in diabetic mice. Taken together,
netrin-1 regulates corneal epithelial wound healing,
inflammation response and nerve fiber regeneration in diabetic mice, indicating the potential application for the
therapy of diabetic keratopathy.