Plasma Exosomal microRNA Profile Reveals miRNA 148a-3p Downregulation in the Mucosal-Dominant Variant of Pemphigus Vulgaris

The mucosal-dominant variant of pemphigus vulgaris (MPV) is an autoimmune disease characterized by oral mucosal blistering and circulating pathogenic IgG antibodies against desmoglein 3 (Dsg3), resulting in life-threatening bullae erosion formation. Recently, microRNAs (miRNAs) have emerged as promising players the diagnosis prognosis several pathological states. For first time, we identified a different expression profile miRNAs isolated from plasma-derived exosomes (P-EVs) MPV patients positive for Dsg3 (Dsg3-positive) compared to healthy controls. Moreover, dysregulated miRNA was confirmed tissue biopsies. In particular, strong downregulation miR-148a-3p level P-EVs controls demonstrated. Bioinformatics prediction analysis identifies metalloproteinase-7 (MMP7) potential target. An vitro acantholysis model revealed that dramatically downregulated after treatment with autoantibodies, concomitant increase MMP7 expression. increased leads disruption intercellular and/or extracellular matrix adhesion cellular MPV, subsequent cell dissociation. Overexpression prevented dissociation regressed upregulation. Our findings suggest pivotal role P-EV cargo regulating molecular mechanisms involved pathogenesis indicate them therapeutic targets.