Genomic analysis in the colon tissues of omega-3 fatty acid-treated rats identifies novel gene signatures implicated in ulcerative colitis.

Several long-term intervention trials only studied the ex vivo immunological function to elucidate the beneficial
mechanisms of n-3 polyunsaturated fatty acids (PUFA) in the ulcerative colitis (UC). An unbiased wholetranscriptome
analysis would be more valuable to obtain a comprehensive understanding of the processes and
genes regulated by n-3 PUFA in vivo. In this study, we have performed microarray analysis in the colon tissues of
dextran sulfate sodium (DSS)-induced UC in rats supplemented with n-6 PUFA, n-3PUFA and long-chain n-
3PUFA (LC-n3PUFA). We have identified the novel gene signatures previously not linked to colitis such as Etv3,
Clec4d, CD180, CD72, Megf11, and Angptl4 which are most downregulated in both n-3PUFA and LC-n3PUFA
groups compared to the n-6PUFA group. The most upregulated genes were Nr1i3, Nptx2, and Zfp810 in both
n-3PUFA and LC-n3PUFA groups. The RT-PCR analysis confirmed similar results. Interestingly, LPS treatment in
macrophages upregulated the Megf11, Etv3, CD180, and Angptl4, and correlated with increased secretion of
cytokines. Gene silencing of Etv3, Megf11, and CD180 in rats using intravascular delivery of siRNA-lipoparticles
attenuated the DSS-induced ulceration and mucosal damage. Thus, our genome-wide microarray analysis
identified novel genes regulated by omega-3 PUFA and offers new drug targets that could prevent or reduce UC.