Epithelium-derived exosomal dipeptidyl peptidase-4 involved in arecoline-induced oral submucous fibrosis

Abstract

Introduction

Dipeptidyl peptidase-4 is known to be involved in the progression of several fibrogenic diseases, but its association with oral submucous fibrosis remains unclear. This study aims to ascertain whether dipeptidyl peptidase-4 plays a role in the pathogenesis of arecoline-induced oral submucous fibrosis.

Methods

We assessed the expression of dipeptidyl peptidase-4 in arecoline-treated epithelial cells and the exosomes derived from cells. We cocultured the fibroblast and exosomes derived from epithelium cells and assessed fibrogenic activity by measuring collagen secretion, α-SMA expression, and gel contraction capability. An animal study was conducted to confirm the fibrogenic activity of exosomes derived from arecoline-treated epithelial cells. Additionally, we employed a dipeptidyl peptidase-4 inhibitor to assess its efficacy in mitigating fibrogenesis.

Results

Following arecoline treatment, an increase dipeptidyl peptidase-4 expression was observed in exosomes from the treated epithelium cells. When these exosomes cocultured with fibroblast, fibrogenic gene α-SMA was upregulated, increased collagen secretion, and enhanced gel contraction capability. In a mouse model, the administration of arecoline-treated epithelium-derived exosomes induced oral submucous fibrosis phenotype, characterized by a reduction in incisal distance and epithelial atrophy.

Conclusions

These findings offer valuable insights into clinical strategies for combating oral fibrotic disease and contribute to the foundation of future research in this field.