ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 530

Downregulation of Microrna-183 in Sjogren’s Syndrome Minor Salivary Glands. Implications in Control of Ezrin Expression and Salivary Gland Function

Paola Perez Riveros1, Mayank Tandon1, Salman Kazmi2, Alessia Gallo2, Gabor G. Illei3 and Ilias Alevizos4, 1Sjogren's Clinic, NIDCR, Bethesda, MD, 2NIH, Bethesda, MD, 3Sjogren's Clinic, NIDCR/ NIH, Bethesda, MD, 4Sjogren's Clinic, NIDCR/ NIH #10 1N110, Bethesda, MD

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Sjogren's Syndrome: Pathophysiology

Session Type: Abstract Submissions (ACR)

Background/Purpose

Sjogren’s syndrome (SS) is an exocrinopathy, which is mainly characterized by salivary glands (SG) hypofunction. SGs from SS patients present dilated lumen in acini and loss of microvilli in the acinar cell SG. Previously, we reported that these changes correlate with an aberrant location in the basal pole of the acinar cells and an overexpression of ezrin. Ezrin is a cytoplasmic peripheral membrane protein that regulates the microvilli organization and secretion of exocrine cells. The mechanism of gene expression and specific function of ezrin in SG is unknown. We also proved that microRNA hsa-miR-183 is down regulated in SG from SS patients and it can modify the expression of ezrin SG cell culture in 3D. Here we are further confirming the function of hsa-miR-183 in vivo, its implication in saliva secretion and exploring a mechanism by which ezrin mislocalization produce saliva hyposecretion.

Methods

LNA-antimir-183 was transfected into mice parotid SG. The effect of the blockage of hsa-mir-183 was assessed evaluating the volume of saliva secretion after stimulation with isoproterenol and ezrin protein expression. Proximity ligation assay was performed to determine the interaction of ezrin with three possible targets: Sodium-hydrogen antiporter 3-regulator1 (SLC9A3R1), Anotacmin1 (ANO1) and Rab27A.

Results

The in vivo transfection of the LNA-antimir produced an increase of protein levels of ezrin and a decrease in the saliva secretion. ANO1 did not appear to form complex with ezrin in human SG. The complex ezrin/SLC9A3R1 was decreased in apical pole acinar cells of SS patient. A similar change was observed for ezrin/Rab27.

Conclusion

These experiments suggest that in SG of SS patients the overexpression of ezrin is produced by the down regulation hsa-miR-183 and propose a role of ezrin in the mechanism of SG hyposecretion. In this mechanism the mislocalization of ezrin affect the localization of the sodium-hydrogen antiporter 3-regulator1, altering the activation of the SLC9A3R1 and the electrolyte balance to regulate water secretion. Additionally, the change in the interactionof ezrin- Rab27A would affect the fusion of the secretory granules with apical plasma membrane.

Disclosure:

P. Perez Riveros,
None;

M. Tandon,
None;

S. Kazmi,
None;

A. Gallo,
None;

G. G. Illei,
None;

I. Alevizos,
None.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/downregulation-of-microrna-183-in-sjogrens-syndrome-minor-salivary-glands-implications-in-control-of-ezrin-expression-and-salivary-gland-function/