AB0401 ASSESSMENT OF GENES INVOLVED IN SJÖGREN’S SYNDROME RELATED XEROSTOMIA
Authors: K. Błochowiak, P. Celichowski, K. Iwanik, M. Nowicki, B. Kempisty
Journal: Annals of the Rheumatic Diseases (2020)

Background: Sjögren’s syndrome (SS) is characterized by decreased saliva secretion. It is regulated mainly by parasympathetic nervous system. The genes involved in xerostomia can play a neuroprotective role [1]. The expression profiling is helpful to understand the mechanisms of SS related xerostomia. Objectives: We aimed to investigate and compare gene expression in labial salivary glands from SS patients with xerostomia SS(+) and without xerostomia SS(-) and healthy subjects (HS) by microarray analysis and to find genes potentially involved in xerostomia. Methods: The study group comprised 11 SS patients (3 SS(+) and 8 SS(-)) and 9 HS. Labial salivary gland samples were processed according to the protocol [2]. Database for Annotation, Visualization and Integrated Discovery (DAVID) and Search Tool for the Retrieval of Interacting Genes (STRING10) were used for the interactions between study groups [3]. Results: Among the genes belonging to “secretion” ontology group, expression of Amyloid Beta Precursor Protein (APP) and Cholinergic Receptor Muscarinic 3 (CHRM3) in both SS(+) and SS(-) groups were lower than in HS. The expression of Visinin Like 1 (VSNL1) in SS(+) and SS(-) was higher than in HS. The expression of Serum Amyloid A1 (SAA1) and Amyloid Beta Precursor like Protein 2 (APLP2) were decreased in SS(+) group and increased in SS(-) compared to HS group. There was no differences between the SS(+) and SS(-) in expression of mentioned genes. Table 1. Fold changes, adjusted p values of differentially expressed genes in SS(+) and SS(-) groups Gene symbol Ratio SS(-) Ratio SS(+) adjusted p.value.SS(-) adjusted p.value.SS(+) APP -1,230085 -4,00201 0,9824056 0,00029089 SAA1 1,446255611 -2,222329225 0,831872232 0,046639694 APLP2 1,118778 -2,232646 0,9121355 0,01132797 CHRM3 -1,745830276 -5,359431593 0,867931575 0,000023 VSNL1 1,608504852 3,127527026 0,916228964 0,000513257 Figure 1. STRING-generated interaction network among differentially expressed genes belonging to the „secretion” ontology group. Conclusion: Decreased expression of APP, SAA1, APLP2 and CHRM3 in SS(+) sufferers compared to HS can reflect the loss of their neuroprotective function and the cholinergic deficiency in xerostomia. STRING10 software indicates for a cenral role of APP and genes involved in β-amyloid peptide formation and neurodevelopment and for a close relationships between SS and neurodegenerative diseases [4,5]. References: [1]Bhattarai KR, Junjappa R, Handigund M, et al. The imprint of salivary secretion in autoimmune disorders and related pathological conditions. Autoimmunity Reviews. 2018, 17:376-390 [2]Celichowski P, Nawrocki MJ, Dyszkiewicz-Konwińska M, et al. „Positive regulation of RNA metabolic proces” ontology group highly regulated in porcine oocytes matured in vitro: a microarray approach. BioMed Research International 2018, ID2863068. [3]Von Mering C, Jensen LJ, Snel B. „STRING: known and predicted protein-protein associations, integrated and transffered across organisms” Nucleic Acids Research. 2005, 33, suplement 1, pp DD433-D437. [4]Montibeller L, de Belleroche J. Amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD) are characterised by differentia activation of ER stress pathways: Focus on UPR target genes. Cell Stress and Chaperones. 2018, 23:897-912. [5]Fisher A, Pittel Z, Haring R, et al. M1 Muscarinic Agonists can modulate some of the hallmarks in Alzheimer’s disease. J Molecular Neuroscience. 2003, 20:349-356. Disclosure of Interests: None declared