Project description:Voglibose is an α-glycosidase inhibitor with anti-inflammatory effects on the intestine, but the underlying mechanism is not clear. Our study defined the dynamic changes of the differentially expressed genes after treatment of voglibose in diabetic KKAy mice, and provide basis for comprehensive understanding of the disease at molecular level. We investigated gene expression alteration after a long-term treatment of voglibose in diabetic KKAy mice.
Project description:The novel Traditional Chinese Medicine Ramulus Mori (Sangzhi) alkaloid tablets (SZ-A) are approved by The China National Medical Products Administration for the treatment of type 2 diabetes mellitus (T2DM). However, the extensive pharmacological characteristics and the underlying mechanism are unknown. This study investigated the mechanisms by which SZ-A ameliorates glucose metabolism in KKAy mice, an animal model of T2DM. Diabetic KKAy mice were treated intragastrically with SZ-A once daily for 8 weeks, after which glucose levels, lipid metabolism, gut microbiome, systemic inflammatory factors, luminal concentrations of short-chain fatty acids (fecal samples), and ileal proteomic changes were evaluated. The ileum tissues were collected, and the effects of SZ-A on pathological inflammatory damage were evaluated by hematoxylin and eosin staining, immunofluorescence, and immunohistochemistry. The mRNA and protein expression levels of various inflammatory markers, including monocyte chemoattractant protein-1 and phosphorylated nuclear factor kappa B p65, were detected in the ileum tissues. SZ-A improved glucose metabolism with enhanced insulin response and elevated glucagon-like peptide 1 (GLP-1) during the glucose tolerance test in diabetic KKAy mice. Gut microbiota analysis demonstrated that SZ-A administration elevated the abundance of Bacteroidaceae and Verrucomicrobia, reduced the levels of Rikenellaceae and Desulfovibrionaceae; and increased the concentrations of fecal acetic and propionic acids compared to the diabetic model group. Additionally, SZ-A markedly improved ileal inflammatory injury and pro-inflammatory macrophage infiltration and improved intestinal mucosal barrier function in diabetic KKAy mice. SZ-A also attenuated the levels of circulating endotoxin, pro-inflammatory cytokines, and chemokines in the mice sera. Collectively, SZ-A ameliorated the overall metabolic profile including glucose and lipid metabolism in KKAy mice, which may be associated with an improvement in GLP-1 and insulin secretion, at least in part by modulating the gut microbiome and relieving the degree of ileal and systemic inflammation.
Project description:GATA6 is a transcription factor involved in the differentiation of intestinal epithelial cells into differentiated absorptive epithelial cells. GATA6 is expressed in all segments of the small intestine. We examined the impact of deleting GATA6 from intestinal epithelial cells of the adult ileum 6-8 week old Villin-CreERT2 mice or Villin-CreERT2 mice crossed to GATA6 flox/flox mice were treated with a single injection of tamoxifen. (100 mg/ml) for 5 consecutive days. 28 days later the ileum was dissected and RNA prepared from the whole ileal segment using the RNAeasy method with DNAse treatment. Three individual mice were examined in each of the control and GATA6 KO groups.
Project description:Determination of differentially expressed genes in the proximal colon and distal ileum tissue in MR1 and IL-17A deficiency at steady-state. Tissue from naïve mice was harvested, total RNA extracted and subjected to RNASeq analysis.
Project description:This study aimed to investigate the effects of depression on transcriptome in ileum using a subchronic and mild social defeat stress (sCSDS) model. In addition to exhibiting social deficit and hyperphagia-like behavior, the sCSDS mice keep much more water in their body than control mice. In order to investigate the effect of social defeat stress on not only central nervous system but also function of gastrointestinal tract, the gene expression in ileum of stressed mice was compared with control mice. We used microarrays to detail the gene expression after 10 days of social defeat stress and identified distinct classes of down-regulated genes during this process.