Integrin alpha v beta 6 contributes to maintaining corneal epithelial barrier function

Abstract

The corneal epithelial barrier dysfunction is associated with a number of disorders of the cornea. This study aims to investigate the role of integrin alpha v beta 6 (avb6) in maintaining the corneal epithelial barrier function. In this study, the association of avb6 and endosome/lysosome in the human corneal epithelial cell line, HCE cells, was observed with immunocytochemistry. The corneal epithelial barrier function was assessed with HCE monolayers in Transwells. The results showed that avb6 was observed attaching to endosomes in HCE cells. Knockdown of avb6 resulted in disturbing the fusion of endosome/lysosome. Tumor necrosis factor (TNF)-α could bind avb6 to form a complex that interfered with the fusion of endosome/lysosome in HCE cells. With the HCE monolayer as a corneal epithelial barrier model, the knockdown of avb6 or exposure to TNF-α markedly increased the epithelial barrier permeability to a macomolecular protein, ovalbumin, in Transwell system. After passing through the deficient epithelial barrier, the ovalbumin molecules still conserved the antigenicity. We conclude that the integrin avb6 plays an important role in the fusion of endosome/lysosome in corneal epithelial cells; inhibition of avb6 results in corneal epithelial barrier dysfunction.

Alphavbeta6 is required in maintaining the intestinal epithelial barrier function

“…avb6 also contributes to the pathogenesis of cancer (Bates, ). Our data add novel information to another aspect of avb6 by showing that avb6 is required in the degradation of the endocytic antigens in T84 cells, which is in accord with Guo et al () who showed that avb6 is involved in tethering the endosome and lysosome in corneal epithelial cells.…”

“…Fischer et al () found adalimumab (an anti‐TNF‐α antibody) prevents barrier dysfunction induced by TNF‐α both functionally and structurally, as well as at the level of signal transduction. Cell‐based therapy has been attempted to repair the airway epithelial barrier dysfunction in animal studies (Bhattacharya and Matthay, ), and exposure to TNF‐α inhibits avb6 in corneal epithelial cells (Guo et al, ). We have now shown that addition of recombinant avb6 abolishes TNF‐α‐induced T84 monolayer barrier dysfunction.…”

“…Integrin alphavbeta6 (avb6 hereafter) is involved in the fusion of endosome and lysosome in corneal epithelial cells (Guo et al, ). Avb6 is a member of the integrin family, which are transmembrane receptors that mediate the cell‐cell attachment and their surrounding structures.…”

The timing of human adaptation from Neanderthal introgression

“…HELZ2 is involved in regulating the differentiation of adipocytes and could thus play a role in metabolism (Katano-Toki et al, 2013). PLA2R1, ITGB6, and SLIT3 putatively play a role in tumor suppression, however mutations at all of these loci are also known to influence variation in other phenotypes (Marlow et al, 2008; Hezel et al, 2012; Guo et al, 2013; Bernard and Vindrieux, 2014; Yu et al, 2014; Ng et al, 2018; Yoshikawa and Asaba, 2020). Most research on RHPN2 and PTK6 has focused on the role of their expression in cancer progression (e.g.…”

Drug-peptide supramolecular hydrogel boosting transcorneal permeability and pharmacological activity via ligand-receptor interaction

“…Meanwhile, the utilization of peptides confers a great degree of functionality to a hydrogel and allows active targeting of a particular receptor on the desired cells. Given that several integrins are widely expressed on all nucleated cells including corneal epithelial cells, phagocytic cells [ [33] , [34] , [35] , [36] ], we rationally designed and synthesized an integrin-targeted drug-peptide conjugate based on Arg-Gly-Asp (RGD) motif. This drug-peptide conjugate formed supramolecular hydrogel spontaneously in phosphate buffered saline (PBS; pH = 7.4) without external stimuli, endowing its great applicability for topical ocular drug delivery.…”