Pepsin Increases the Proliferation of Vocal Cord Leukoplakia Epithelial Cells by Inducing Autophagy

Abstract

Objective: To investigate the role of H⁺ /K⁺ ATPase in the proliferation of pepsin-induced vocal cord leukoplakia (VCL) cells.

Study design: Translation research.

Setting: Affiliated Hospital of University.

Methods: Immunohistochemistry was used to detect pepsin, H⁺ /K⁺ ATPase (ATP4A and ATP4B subunits) in VCL cells with varying degrees of dysplasia. After primary cultures of VCL cells had been established, the effects of acidified pepsin on the proliferation, autophagy, and H⁺ /K⁺ -ATPase distribution of VCL cells were investigated.

Results: The levels of pepsin, ATP4A, and ATP4B were significantly higher in VCL tissue with moderate-to-severe dysplasia than in normal tissue (p < .05); these levels gradually increased according to dysplasia severity. The expression levels of ATP4A and ATP4B were significantly correlated with the amount of pepsin in VCL cells (p < .01). Acidified pepsin enhanced the levels of proliferation and autophagy in human VCL epithelial cells. The cloning- and autophagy-promoting effects of acidified pepsin on VCL cells were partially reversed by pantoprazole; these effects were completely blocked by the autophagy inhibitor chloroquine. Finally, acidified pepsin promoted the colocalization of H⁺ /K⁺ -ATPase and lysosomes in VCL cells; it also mediated lysosome acidification.

Conclusion: Pepsin and H⁺ /K⁺ -ATPase may contribute to the progression of VCL. Specifically, acidified pepsin may regulate lysosome acidification by promoting lysosomal localization of H⁺ /K⁺ -ATPase.

Keywords: H+/K+-ATPase; LC3; P62; autophagy; lysosome acidification; pepsin; vocal cord leukoplakia.