Protein disulfide isomerase family A member 3 expression is upregulated in tissue-derived extracellular vesicles in oral lichen planus and oral lichenoid lesions

Abstract

ObjectivesThe aim of this study was to identify the tissue-derived extracellular vesicles immunogen involved in the pathogenesis of oral lichen planus (OLP) and its variation oral lichenoid lesions (OLL). DesignSix pooled tissue-derived extracellular vesicles from participants with OLP/OLL and three from healthy controls were isolated and enriched. The extracellular vesicles were characterized with transmission electronic microscopy, nanoparticle tracking analysis and western blotting. Proteins from extracellular vesicles were identified with proteomics analysis and differentially expressed proteins (DEPs) were further identified with a 2-fold (p < 0.05) increase or a 0.5-fold decrease. ResultsA total of 1805 peptides and 141 proteins were identified. Ten DEPs were further identified, with five upregulated proteins of fibrinogen alpha chain, lamin isoform A, 40S ribosomal protein, protein disulfide isomerase family A member 3 (PDIA3) and elongation factor 1-alpha 1, and five downregulated proteins of plakophilin-1, katanin p80 repeat-containing subunit B1, collagen alpha-3 chain, mitochondrial 2-oxoglutarate/malate carrier protein and guanine nucleotide-binding protein subunit gamma-12. PDIA3 was found to be immune-associated and to be involved in the antigen processing and presentation pathway. The upregulation of PDIA3 was confirmed in a verification cohort composed of three pairs of OLP/OLL-extracellular vesicles and healthy controls-extracellular vesicles with western blotting. ConclusionsProtein disulfide isomerase family A member 3 in extracellular vesicles may play a significant role in the local immune responses and the pathogenesis of oral lichen planus and oral lichenoid lesions.