WGCNA Reveals Key Roles of IL8 and MMP-9 in Progression of Involvement Area in Colon of Patients with Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is a chronic inflammatory disease and its involvement area in colon is influenced by a complex network of gene interactions. We analyzed the weighted gene co-expression networks in microarray dataset from colonic mucosa of patients with UC and identified one gene co-expression module that was highly associated with the progression of involved area in UC colon (Pearson coefficient=0.81, P<0.0001). In total, 523 hub genes in this module were found to be involved in immune system process after enrichment analysis in Gene Ontology. By the STRING and Cytoscape analysis, we observed that interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) were centered in the network of hub genes. We then detected the expression of IL-8 and MMP-9 in mucosa from left-sided colon of patients using quantitative PCR and immunofluorescence assay respectively. Both quantitative PCR and immunofluorescence assay revealed the expression levels of IL-8 and MMP-9 were significantly different among the healthy controls, left-sided colitis group and pancolitis group (P<0.05). IL-8 and MMP-9 were detected with an enhanced expression in pancolitis as compared with leftsided colitis and healthy controls, respectively (P<0.05). This study demonstrates that immune system process is indispensable in the progression of disease in colon, and identifies that IL-8 and MMP-9 play potential critical roles for the progression.

Keywords

ulcerative colitis / weighted gene co-expression network analysis / interleukin-8 / matrix metalloproteinase-9

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