Nuclear translocation of β-catenin induced by E-cadherin endocytosis causes recurrent erosion of diabetic cornea.

Abstract

Recurrent epithelial erosion and refractory corneal ulcer are the clinical features of diabetic keratopathy (DK), which eventually lead to corneal scar and visual disturbance. In this study, we sought to determine the abnormalities of cell junction in diabetic corneal epithelial cells and the effect of high glucose on the β-catenin/E-cadherin complex. Corneal histology showed that corneal epithelial cells of high glucose mice were loosely arranged, and the immunohistochemistry showed that the expression of E-cadherin decreased, the levels of β-catenin increased in nuclear. High glucose-induced degradation and endocytosis of E-cadherin of corneal epithelial cells reduce the formation of β-catenin/E-cadherin complex and promote the nuclear translocation of β-catenin. Moreover, high glucose also activated the transcription and expression of matrix metallopeptidase and snail, which interfered with the adhesion of corneal epithelial cells to the basement membrane. These findings reveal that DK is associated with the dissociation of cell junctions. The maintenance of the stability of the β-catenin/E-cadherin complex may be a potential therapeutic target of refractory corneal ulcers in patients with diabetes.