Project description:Atoh1 is the master transcription factor of secretory-type intestinal epithelial cells. By using a lineage-tracing model of Atoh1+ve cells, those Atoh1+ve epithelial cells and their descendants were collected from the colon of DSS-colitis mice or from the control mice, and subjected to global gene expression analysis.
Project description:Colonic gene expression profiles of mice with DSS-induced colitis treated with apple peel polyphenolic extract Four-condition experiment: control, DSS-induced colitis, and mice treated with DAPP (two different doses (200 and 400 mg/kg/day) before or during induction and development of DSS-induced colitis.
Project description:Atoh1 is the master transcription factor of intestinal secretory cells. Lineage-tracing model of Atoh1+ve cells showed that the progeny of Atoh1+ve cells can develop into either LGR5+ve or LGR5-ve cells. Present analysis compared the gene expression profile of Atoh1+ve cell-derived LGR5+ve cells and LGR5-ve cells, compared to the resident LGR5+ve cell population of the mouse small intestine.
Project description:Primary cilia (PC) are important signaling hubs in cells and we explored their role in colorectal cancer (CRC) and colitis. In the colon we found PC to be mostly present on different subtypes of fibroblasts and exposure of mice to either chemically induced colitis-associated colon carcinogenesis (CAC) or dextran sodium sulfate (DSS)-induced acute colitis decreased PC numbers. We employed conditional knock-out strains for the PC essential genes, Kif3A and Ift88, to generate mice with reduced numbers of PC on colonic fibroblasts. These mice showed an increased susceptibility in the CAC model as well as in DSS-induced colitis. Secretome and immunohistochemical analyses of DSS-treated mice displayed an elevated production of the pro-inflammatory cytokine IL-6 in PC-deficient colons. An inflammatory environment diminished PC presence in primary fibroblast cultures. This was triggered by IL-6 as identified by RNAseq analysis together with blocking experiments, suggesting an activation loop between IL-6 production and PC loss. Notably, an analysis of PC presence on biopsies of patients with ulcerative colitis as well as CRC patients revealed decreased numbers of PC on colonic fibroblasts in pathological versus surrounding normal tissue. Taken together, we provide evidence that a decrease in colonic PC numbers promotes colitis and CRC.
Project description:Background and Aims. Dendritic cells (DCs) play a pivotal role in maintaining immunological homeostasis by orchestrating innate and adaptive immune responses via migration to inflamed sites and the lymph nodes (LNs). Plasmacytoid DCs (pDCs) have been reported to accumulate in the colon of inflammatory bowel disease (IBD) patients and dextran sulfate sodium (DSS)-induced colitis mice. However, the role of pDCs in the progression of colonic inflammation remains unclear. Methods. 80 compounds in natural medicines were searched for inhibitors of pDC migration using bone marrow-derived pDCs (BMpDCs) and conventional DCs (BMcDCs). BALB/c mice were given 3% DSS in the drinking water for 7 days to induce acute colitis. Compounds, which specifically inhibited pDC migration, were administrated into DSS-induced colitis mice. Results. Astragaloside IV (As-IV) and oxymatrine (Oxy) suppressed BMpDC migration but not BMcDC migration. In DSS-induced colitis mice, the number of pDCs was markedly increased in the colonic lamina propria (LP), and the expression of CCL21 was obviously observed in colonic isolated lymphoid follicles (ILFs). As-IV and Oxy reduced symptoms of colitis and the accumulation of pDCs in colonic ILFs but not in the colonic LP. Moreover, in a BMpDC adoptive transfer model, BMpDC migration to colonic ILFs was significantly decreased by treatment with As-IV or Oxy. Conclusion. pDCs accumulated in the colon of DSS-induced colitis mice, and As-IV and Oxy ameliorated DSS-induced colitis by suppressing pDC migration to colonic ILFs. Accordingly, the selective inhibition of pDC migration may be a potential therapeutic approach for treating colonic inflammatory diseases.
Project description:B cells expand during the recovery after DSS-induced colonic inflammation and might play a role in influencing tissue repair. To analyze the impact B cells might have on intestinal epithelial cells and stromal cells during recovery after intestinal injury the transcriptional profile of these mice was analysed in mice depleted of B cells and control mice on day 14 after DSS colitis.
Project description:The aim of this study is to compare the transcriptomic profile of colonic intestinal epithelial cells (IECs) at steady-state, and in several models of colitis: in naive wild-type C57BL/6 mice, in wild-type C57BL/6 mice treated for 7 days with 3% dextran sodium sulfate (DSS) in drinking water, in Il10-/- C57BL/6 mice and Il10-/- C57BL/6 mice with IEC-specific Rabgef1 deletion. Colonic IECs were isolated and FACS-sorted, then subjected tu bulk RNA-seq.
Project description:To identify potential unique miRs that contribute to shaping the intestinal stemness in colitis, we analyzed the miRNome of colonic crypt stem cells from DSS-induced colitis mice.
Project description:TMT proteomics for colonic mucosa in DSS-induced colitis mice with or without administrated Cyanidin-3-O-glucoside was used for discovery of differential expressed proteins.
