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Recently, microRNAs (miRNAs) have emerged as promising players in the diagnosis and prognosis of several pathological states. For the first time, we have identified a different expression profile of miRNAs isolated from plasma-derived exosomes (P-EVs) of MPV patients positive for antibodies against Dsg3 (Dsg3-positive) compared to healthy controls. Moreover, a dysregulated miRNA profile was confirmed in MPV tissue biopsies. In particular, a strong downregulation of the miR-148a-3p expression level in P-EVs of MPV patients compared to healthy controls was demonstrated. Bioinformatics prediction analysis identifies metalloproteinase-7 (MMP7) as a potential miR-148a-3p target. An in vitro acantholysis model revealed that the miR-148a-3p expression level was dramatically downregulated after treatment with Dsg3 autoantibodies, with a concomitant increase in MMP7 expression. The increased expression of MMP7 leads to the disruption of intercellular and\/or extracellular matrix adhesion in an in vitro cellular model of MPV, with subsequent cell dissociation. Overexpression of miR-148a-3p prevented cell dissociation and regressed MMP7 upregulation. Our findings suggest a pivotal role of P-EV cargo in regulating molecular mechanisms involved in MPV pathogenesis and indicate them as potential MPV therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms241411493","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T00:35:04Z","timestamp":1689554104000},"page":"11493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Plasma Exosomal microRNA Profile Reveals miRNA 148a-3p Downregulation in the Mucosal-Dominant Variant of Pemphigus Vulgaris"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8041-2221","authenticated-orcid":false,"given":"Anna","family":"Valentino","sequence":"first","affiliation":[{"name":"Research Institute on Terrestrial Ecosystems (IRET)\u2014CNR, Via Pietro Castellino 111, 80131 Naples, Italy"},{"name":"National Biodiversity Future Center (NBFC), 90133 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4468-5083","authenticated-orcid":false,"given":"Stefania","family":"Leuci","sequence":"additional","affiliation":[{"name":"Oral Medicine Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University of Naples, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0909-7403","authenticated-orcid":false,"given":"Umberto","family":"Galderisi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli\u201d, Via Santa Maria di Costantinopoli, 80100 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3769-9786","authenticated-orcid":false,"given":"Gianrico","family":"Spagnuolo","sequence":"additional","affiliation":[{"name":"Oral Medicine Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University of Naples, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele Davide","family":"Mignogna","sequence":"additional","affiliation":[{"name":"Oral Medicine Unit, Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University of Naples, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Peluso","sequence":"additional","affiliation":[{"name":"Research Institute on Terrestrial Ecosystems (IRET)\u2014CNR, Via Pietro Castellino 111, 80131 Naples, Italy"},{"name":"Faculty of Medicine and Surgery, Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1441-7662","authenticated-orcid":false,"given":"Anna","family":"Calarco","sequence":"additional","affiliation":[{"name":"Research Institute on Terrestrial Ecosystems (IRET)\u2014CNR, Via Pietro Castellino 111, 80131 Naples, Italy"},{"name":"Faculty of Medicine and Surgery, Saint Camillus International University of Health Sciences, Via di Sant\u2019Alessandro 8, 00131 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jid.2022.07.030","article-title":"IgG against the Membrane-Proximal Portion of the Desmoglein 3 Ectodomain Induces Loss of Keratinocyte Adhesion, a Hallmark in Pemphigus Vulgaris","volume":"143","author":"Hudemann","year":"2023","journal-title":"J. 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