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EBioMedicine. 2016 Aug;10:216-26. doi: 10.1016/j.ebiom.2016.06.041. Epub 2016 Jun 29.

Targeting the Ca(2+) Sensor STIM1 by Exosomal Transfer of Ebv-miR-BART13-3p is Associated with Sjögren's Syndrome.

Author information

1
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.
2
Secretory Physiology Section, Molecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, USA.
3
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.

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.

KEYWORDS:

Exosomes; STIM1; Salivary gland dysfunction; Sjögren's syndrome; microRNA

PMID:
27381477
PMCID:
PMC5006644
DOI:
10.1016/j.ebiom.2016.06.041
[Indexed for MEDLINE]
Free PMC Article

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