Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
Background/Purpose: Loss of secretory epithelial function is a hallmark of primary Sjögren’s syndrome (pSS). Previously we reported that bone morphogenetic protein 6 (BMP-6) inhibits cell volume regulation and is associated with the loss of salivary gland dysfunction in human and experimental pSS. The objective of this study is to understand the mechanism associated with BMP-6 induced salivary gland hypofunction and develop a novel treatment based on this to restore salivary flow.
Methods: Correlative gene expression analysis was used to identify gene expression changes that were induced by BMP6 expression. Adeno-associated vector (AAV) mediated AQP-5 and AQP-1 were transferred in BMP-6 treated human salivary gland cell (HSG) lines and membrane water permeability was detected by regulated volume decrease (RVD) assay. AAV mediated AQP-1 was delivered to either BMP-6 overexpression induced xerostomia animal model or C57BL/6.NOD-Aec1Aec2 Sjögren’s mouse model.
Results: Correlation analysis identified AQP-5 expression as changing with BMP-6 induced loss in cellular regulated volume decrease. Confocal imaging confirmed a correlation between an increase in BMP6 expression and a decrease in AQP5 expression. Exogenous expression of AQP-1 or AQP-1 in HSG cells can restore the water permeability that was decreased by BMP-6. Salivary gland AAV-AQP-1 local gene therapy in animal models restored secretory function in both salivary and lacrimal glands, accompanied with decreased sailadenitis and systemic inflammation markers.
Conclusion: AAV mediated AQP-1 local gene therapy in salivary gland is a promising treatment for salivary and lacrimal epithelial hypofunction and systemic symptoms associated with pSS.
To cite this abstract in AMA style:Yin H, Lai Z, Cabrera-Perez J, Glenton P, Patel A, Swaim W, Zheng C, Guimaro M, Afione S, Nguyen C, Nyberg F, Chiorini JA. Aquaporin Gene Therapy Corrects Bone Morphogenetic Protein 6 Associated Exocrine Gland Dysfunction in Mouse Model of Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/aquaporin-gene-therapy-corrects-bone-morphogenetic-protein-6-associated-exocrine-gland-dysfunction-in-mouse-model-of-sjgrens-syndrome/. Accessed January 26, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/aquaporin-gene-therapy-corrects-bone-morphogenetic-protein-6-associated-exocrine-gland-dysfunction-in-mouse-model-of-sjgrens-syndrome/