Temporal genomewide expression profiling of DSS colitis reveals novel inflammatory and angiogenesis genes similar to ulcerative colitis

Abstract

Dextran sodium sulfate (DSS)-induced colitis is widely used to study pathological mechanisms and potential treatments of inflammatory bowel disease. Because temporal changes in genome expression profiles remain unknown in this model, we performed whole genome expression profile analysis during the development of DSS colitis in comparison with ulcerative colitis (UC) specimens to identify novel and common responses during disease. Colon tissue from DSS-treated mice was collected at days 0, 2, 4, and 6. Half of each specimen was used for histopathological analysis and half for Affymetrix whole genome expression profiling and qRT-PCR validation. Genesifter and Ingenuity software analysis was used to identify differentially expressed genes and perform interactive network analysis. Identified DSS-associated genes in mice were also compared with UC patient data. We identified 1,609 genes that were significantly altered during DSS colitis; the majority were functionally related to inflammation, angiogenesis, metabolism, biological adhesion, cellular growth and proliferation, and cell-to-cell signaling responses. Five hundred and one genes were progressively upregulated, while one hundred seventy-three genes were progressively downregulated. Changes in gene expression were validated in a subset of 33 genes by qRT-PCR, with r(2) = 0.925. Ingenuity gene interaction network analysis revealed novel relationships among antigen presentation, cell morphology, and other biological functions in the DSS mouse. Finally, DSS colitis gene array data were compared with UC patient array data: 152 genes were similarly upregulated, and 22 genes were downregulated. Temporal genomewide expression profile analysis of DSS-induced colitis revealed novel associations with various immune responses and tissue remodeling events such as angiogenesis similar to those in UC patients. This study provides a comprehensive view of DSS colitis changes in colon gene expression and identifies common molecules with clinical specimens that are interesting targets for further investigation.

Chromatin Profiling Reveals Regulatory Network Shifts and a Protective Role for Hepatocyte Nuclear Factor 4α during Colitis

“…Consistent with a functional regulatory role, genomic regions that exhibit the most dynamic decrease in enhancer chromatin structure were located near genes with reduced transcript levels upon inflammation (20). Conversely, regions that gained enhancer chromatin signal were near genes with increased expression levels upon inflammation (Fig.…”

“…Gene set enrichment analysis (GSEA) (19) was performed using public gene expression data from DSS-treated mice (GEO series GSE22307; expression data reported for C57BL/6J male mice, 12 to 14 weeks old, treated with 3% DSS for 6 days, and controls, with whole-colon tissue RNA measured using Affymetrix 430_2.0 arrays [20]). These GSE22307 expression data were compared to genes within 10 kb of the 1,000 most positive or 1,000 most negative NSD-scoring chromatin regions.…”

IL-16 Induces Intestinal Inflammation via PepT1 Upregulation in a Pufferfish Model: New Insights into the Molecular Mechanism of Inflammatory Bowel Disease

“…Briefly, the experimental fish were fed twice daily with radiation-sterilized frozen red worms at ∼3% of their body weight. Then, they were administered with 500 ml 5% DSS (molecular mass of [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] kDa; MP Biomedicals) via oral perfusion once a day just before the second feeding time to ensure that the intestines of the fish were empty when they received the drug. The DSS administration was performed for 7 consecutive days to induce colitis.…”

“…It has been reported that DSS treatment leads to superficial inflammatory changes in the mucosa and submucosa of colon tissues in mouse models with various histopathological features similar to that seen in human UC (36,(41)(42)(43)(44)(45). Therefore, the DSS-induced colitis model has become one of the most widely used experimental models for human UC research (42).…”

SDF-1–CXCR4 differentially regulates autoimmune diabetogenic T cell adhesion through ROBO1–SLIT2 interactions in mice

“…RNA isolation and quantitative RT-PCR Quantitative RT-PCR analysis was performed as previously reported by our laboratory [20]. Total RNA was isolated using a kit (RNeasy Isolation Kit; Qiagen, Hilden, Germany).…”