Transcriptomic Profile of Genes Encoding Proteins Involved in Pathogenesis of Sjögren's Syndrome Related Xerostomia-Molecular and Clinical Trial.

Katarzyna Błochowiak,Michał Nowicki,Katarzyna Iwanik,Piotr Celichowski,Bartosz Kempisty

doi:10.3390/jcm9103299

Abstract

Sjögren’s syndrome (SS) is characterized by xerostomia. We aimed to investigate and compare gene expressions in the labial salivary glands of SS patients with xerostomia SS (sicca) and without xerostomia SS (non-sicca) and of healthy subjects (HS) by means of microarray analysis, and to find genes involved in xerostomia. The study group comprised 11 SS patients (3 SS (sicca) and 8 SS (non-sicca)) and 9 HS. The relative gene expression changes were validated with RT-qPCR in the larger study group. Among the differently expressed genes belonging to the “secretion” ontology group with a fold change >2 and with a p value < 0.05, the Transmembrane P24 Trafficking Protein 10 (TMED10), Protein Disulfide Isomerase Family A Member 4 (PDIA4), Calnexin (CANX), Amyloid Beta Precursor Protein (APP), and Transmembrane BAX Inhibitor Motif Containing 6 (TMBIM6) gene expressions in both SS (sicca) and SS (non-sicca) groups were lower than in HS. Significant correlations were observed between TMED10, PDIA4, and CANX gene expression in SS (sicca) patients compared to the controls. There were no differences between the SS (sicca) and SS (non-sicca) study groups in the expression of the aforementioned genes. Results indicate their role in the endoplasmic reticulum system, their overlapping function and the loss of the APP neuroprotective function in xerostomia. It has a multifactorial origin and can be triggered by disturbances to the various signaling pathways in saliva secretion.

Highlights

Sjögren’s syndrome (SS) is a systemic chronic autoimmune disorder characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands, resulting in decreased secretory function of these glands
We aimed to investigate and compare gene expression locally in labial salivary glands (LSG) obtained from SS patients both with and without xerostomia and from healthy subjects by microarray analysis, and to find genes potentially involved in the development of SS related xerostomia
There is a group of genes involved in SS pathology and the changes in their expression can be the consequence of pathological processes accompanying SS

Summary

Introduction

Sjögren’s syndrome (SS) is a systemic chronic autoimmune disorder characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands, resulting in decreased secretory function of these glands. The results of insufficient salivary flow include difficulties in speaking and eating, sores in the soft tissue, increased risk of opportunistic infections in the oral cavity and the increased caries rate [1,2]. SS can trigger systemic changes, the typical feature of SS is a local predominance of the pathological changes in the exocrine glands, such as salivary glands. These changes are representative for all salivary glands. SS is accompanied by a high but differentially ranged prevalence of xerostomia among SS sufferers

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