title: Targeting the Ca(2+) Sensor STIM1 by Exosomal Transfer of Ebv-miR-BART13-3p is Associated with Sjögren's Syndrome.
abstract: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is associated with inflammation and dysfunction of salivary and lacrimal glands. The molecular mechanism(s) underlying this exocrinopathy is not known, although the syndrome has been associated with viruses, such as the Epstein Barr Virus (EBV). We report herein that an EBV-specific microRNA (ebv-miR-BART13-3p) is significantly elevated in salivary glands (SGs) of pSS patients and we show that it targets stromal interacting molecule 1 (STIM1), a primary regulator of the store-operated Ca(2+) entry (SOCE) pathway that is essential for SG function, leading to loss of SOCE and Ca(2+)-dependent activation of NFAT. Although EBV typically infects B cells and not salivary epithelial cells, ebv-miR-BART13-3p is present in both cell types in pSS SGs. Importantly, we further demonstrate that ebv-miR-BART13-3p can be transferred from B cells to salivary epithelial cells through exosomes and it recapitulates its functional effects on calcium signaling in a model system.
authors.affiliation: Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Gallo
authors.affiliation: Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA.
authors.forename: Shyh-Ing
authors.initials: SI
authors.lastname: Jang
authors.affiliation: Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA.
authors.forename: Hwei Ling
authors.initials: HL
authors.lastname: Ong
authors.affiliation: Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA.
authors.forename: Paola
authors.initials: P
authors.lastname: Perez
authors.affiliation: Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA.
authors.forename: Mayank
authors.initials: M
authors.lastname: Tandon
authors.affiliation: Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA.
authors.forename: Indu
authors.initials: I
authors.lastname: Ambudkar
authors.affiliation: Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA.
authors.forename: Gabor
authors.initials: G
authors.lastname: Illei
authors.affiliation: Sjögren's Syndrome and Salivary Gland Dysfunction Unit, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA. Electronic address: alevizosi@nidcr.nih.gov.
authors.forename: Ilias
authors.initials: I
authors.lastname: Alevizos
mesh_terms: D051402:Aquaporin 5 / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001692:Biological Transport; D015536:Down-Regulation; D004847:Epithelial Cells / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D034622:RNA Interference; D012469:Salivary Glands / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000209:etiology* / Q000378:metabolism*; D000071737:Stromal Interaction Molecule 1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D051402:Aquaporin 5; C000611108:EBV-BART10-3p microRNA; D035683:MicroRNAs; D050778:NFATC Transcription Factors; D000071737:Stromal Interaction Molecule 1
keywords: Exosomes; STIM1; Salivary gland dysfunction; Sjögren's syndrome; microRNA