Systems analysis of primary Sjögrens syndrome pathogenesis in salivary glands identifies shared pathways in human and a mouse modelReport as inadecuate




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Arthritis Research and Therapy

, 14:R238

First Online: 01 November 2012Received: 20 March 2012Revised: 05 September 2012Accepted: 07 September 2012

Abstract

IntroductionPrimary Sjögren-s syndrome pSS is a chronic autoimmune disease with complex etiopathogenesis. Despite extensive studies to understand the disease process utilizing human and mouse models, the intersection between these species remains elusive. To address this gap, we utilized a novel systems biology approach to identify disease-related gene modules and signaling pathways that overlap between humans and mice.

MethodsParotid gland tissues were harvested from 24 pSS and 16 non-pSS sicca patients and 25 controls. For mouse studies, salivary glands were harvested from C57BL-6.NOD-Aec1Aec2 mice at various times during development of pSS-like disease. RNA was analyzed with Affymetrix HG U133+2.0 arrays for human samples and with MOE430+2.0 arrays for mouse samples. The images were processed with Affymetrix software. Weighted-gene co-expression network analysis was used to identify disease-related and functional pathways.

ResultsNineteen co-expression modules were identified in human parotid tissue, of which four were significantly upregulated and three were downregulated in pSS patients compared with non-pSS sicca patients and controls. Notably, one of the human disease-related modules was highly preserved in the mouse model, and was enriched with genes involved in immune and inflammatory responses. Further comparison between these two species led to the identification of genes associated with leukocyte recruitment and germinal center formation.

ConclusionOur systems biology analysis of genome-wide expression data from salivary gland tissue of pSS patients and from a pSS mouse model identified common dysregulated biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis.

AbbreviationsAECGAmerican-European Consensus Group

bpbase pair

EULAREuropean League against Rheumatism

GOgene ontology

H and Ehematoxylin and eosin

ILinterleukin

MMmodule membership

PCRpolymerase chain reaction

pSSprimary Sjögren-s syndrome

TNFtumor necrosis factor

WGCNAweighted gene co-expression network analysis.

Electronic supplementary materialThe online version of this article doi:10.1186-ar4081 contains supplementary material, which is available to authorized users.

Steve Horvath, Abu NM Nazmul-Hossain contributed equally to this work.

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