Project description:Increased levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) have been detected in fibrotic strictures in Crohnâs disease. In a murine model of chronic inflammation, fibrosis was associated with an increase in TIMP-1 and inhibition of matrix metalloproteinase (MMP)-mediated degradation. We investigated the effect of TIMP-1 deficiency on the colonic gene expression in acute and chronic murine models of colitis, using whole genome gene expression arrays. Colitis was induced via oral administration of dextran sodium sulphate (DSS) to B6.129S4-Timp1tm1Pds/J knock-out (KO) and C57BL/6J wild-type (WT) mice. Total RNA extracted from snap frozen colon was used to analyze mRNA expression via Affymetrix Mouse Gene 1.0 ST Arrays
Project description:The lack of suitable animal models reflecting chronically relapsing inflammation and tissue remodeling have hindered fibrosis research in inflammatory bowel diseases (IBD). This study investigated changes in connective tissue in a chronic murine model using different cycles of dextran sodium sulphate (DSS) to mimic the relapsing nature of the disease. We used whole gene expression arrays to study differences in colonic gene expression levels between acute and more chronic DSS colitis, Acute and chronic relapsing colonic inflammation was induced in C57BL6 female mice using several cycles of exposure to DSS in drinking water, followed by recovery phases. Total RNA, extracted from snap frozen colon from five mice per condition was used to analyze mRNA expression via Affymetrix Mouse Gene 1.0 ST arrays.
Project description:To explore the underlying mechanisms of NEDD4L in regulating colitis, colonic tissues from DSS-treated Nedd4lf/f VillinCre (IEC KO) mice and Nedd4lf/f (WT) littermates were subjected to RNA-sequencing analysis.
Project description:H3K27me3 statuses were analyzed in normal mouse colonic epithelial cells and in those exposed to DSS-induced colitis, and aberrant changes of H3K27me3 by DSS-induced colitis were identified.
Project description:We determined changes in enhancer chromatin that occur during colonic inflammation, found that dynamic chromatin regions are enriched for HNF4A binding motirfs, and then measured HNF4A binidng by ChIP-seq in each condition. Examination of H3K27ac histone modification in normal and DSS-treated colon, examination of HNF4A binding by ChIP-seq in normal and DSS-treated colon epithelium
Project description:The lack of suitable animal models reflecting chronically relapsing inflammation and tissue remodeling have hindered fibrosis research in inflammatory bowel diseases (IBD). This study investigated changes in connective tissue in a chronic murine model using different cycles of dextran sodium sulphate (DSS) to mimic the relapsing nature of the disease. We used whole gene expression arrays to study differences in colonic gene expression levels between acute and more chronic DSS colitis,
Project description:Oral administration of dextran sulfate sodium (DSS) to mice induces ulceration and inflammation in the colons of mice. These changes are somewhat similar to those seen in human inflammatory bowel disease. Here we provide a full transcriptome (RNA-Seq) analysis of different gastrointestinal tissues in the regions affected by the DSS chemical, at different timepoints during the injury-inflammation-recovery cycle. The profiled regions include the distal colon (rectum), where the histological changes are most pronounced, the mid-colon, the anus, which is relatively resistant to damage, and the squamous neo-epithelium of the colon, a skin-like tissue that is found in the colon and is believed to be associated with wound healing. We find that administration of DSS is associated with upregulation of cytokines and inflammatory markers. Moreover, stem cell markers of the homeostatic colonic epithelium are depleted, consistent with reprogramming of epithelia to adopt a wound-healing phenotype. Thus, this dataset faithfully recovers broad changes in gene expression in a mouse model of inflammatory bowel disease-like damage.
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.
