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Aquaporin gene therapy corrects Sjogren's syndrome phenotype in mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Natl Inst Dent & Craniofacial Res, Adenoassociated Virus Biol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA..
Natl Inst Dent & Craniofacial Res, Adenoassociated Virus Biol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA..
Natl Inst Dent & Craniofacial Res, Adenoassociated Virus Biol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA..
Natl Inst Dent & Craniofacial Res, Adenoassociated Virus Biol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA..
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2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 20, 5694-5699 p.Article in journal (Refereed) PublishedText
Abstract [en]

Primary Sjogren's syndrome (pSS) is a chronic autoimmune disease that is estimated to affect 35 million people worldwide. Currently, no effective treatments exist for Sjogren's syndrome, and there is a limited understanding of the physiological mechanisms associated with xerostomia and hyposalivation. The present work revealed that aquaporin 5 expression, a water channel critical for salivary gland fluid secretion, is regulated by bone morphogenetic protein 6. Increased expression of this cytokine is strongly associated with the most common symptom of primary Sjogren's syndrome, the loss of salivary gland function. This finding led us to develop a therapy in the treatment of Sjogren's syndrome by increasing the water permeability of the gland to restore saliva flow. Our study demonstrates that the targeted increase of gland permeability not only resulted in the restoration of secretory gland function but also resolved the hallmark salivary gland inflammation and systemic inflammation associated with disease. Secretory function also increased in the lacrimal gland, suggesting this local therapy could treat the systemic symptoms associated with primary Sjogren's syndrome.

Place, publisher, year, edition, pages
2016. Vol. 113, no 20, 5694-5699 p.
Keyword [en]
aquaporin, gene therapy, Sjogren's syndrome
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-297780DOI: 10.1073/pnas.1601992113ISI: 000375977600059PubMedID: 27140635OAI: oai:DiVA.org:uu-297780DiVA: diva2:943637
Funder
NIH (National Institute of Health)NIH (National Institute of Health), DE023433NIH (National Institute of Health), DE018958
Available from: 2016-06-28 Created: 2016-06-28 Last updated: 2016-06-28Bibliographically approved

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Nyberg, Fred
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