Methods: Human parotid glands were harvested from 24 pSS and 16 non-pSS sicca patients following 2002 American-European Consensus Group criteria, and 25 matched controls. Mouse parotid, submandibular and sublingual glands were pooled from C57BL/6.NOD-Aec1Aec2 mice that developed SS-like disease. cRNA was hybridized to Affymetrix U133+2.0 arrays for human and GeneChip 430+2.0 arrays for mouse samples. The resulting gene expression data were subjected to weighted gene co-expression network analysis (WGCNA) that identified color-coded modules enriched with genes and functional pathways.
Results: Seven of the 19 gene-modules identified in humans were significantly different between pSS and control. A highly significant positive correlation was observed between disease status and Magenta (576 genes), Brown (2502 genes), Grey60 (216 genes) and Light-Cyan (349 genes) modules (r=0.67, p<2E-7; r=0.60, p<6E-6; r=0.47, p<8E-4; r=0.42, p<0.002, respectively), suggesting that these modules are comprised of genes that are overexpressed in pSS. Conversely, a highly significant negative correlation was observed with Turquoise (3981 genes), Grey (3011 genes) and Salmon (446 genes) modules (r=-0.52, p<E-4; r=-0.41, p<0.003; r=-0.28, p<0.005, respectively), suggesting that these are comprised of genes that are underexpressed in pSS. Strikingly, the human Magenta module was the most highly preserved module in mouse (p<E-18). This module was enriched with genes involved in immune and inflammatory response, and the IL-4 signaling pathway that has been implicated in pSS disease progression.
Conclusions: Systems biology analysis of human and mouse gene expression data identified common biological pathways and molecular targets underlying critical molecular alterations in pSS pathogenesis.
Keywords: Gene expression, Pathogenicity, Salivary dysfunction, Salivary glands and Systems biology
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