Project description:Iron is an essential cellular and important for many physiological functions including erythropoiesis and host defense. It is taken up from the diet in the duodenum, the first part of the small intestine by enterocytes and loaded onto transferrin, the main iron transport molecules in the circulation. Macrophages are ancient sentinel cells that are implicated in all steps of systemic iron metabolism except duodenal iron import. By assessing mice that harbor a macrophage-specific deletion of the tuberous sclerosis complex 2 (Tsc2), a negative regulator of mTORC1, we found that these mice possessed various defects in iron metabolism including defective steady state erythropoiesis and a highly reduced saturation of transferrin with iron. This iron-deficiency phenotype was caused by a block of iron import from the duodenal epithelial cells into the circulation. Activation of mTORC1 in villous duodenal CD68+ macrophages induced expression of serine proteases and promoted local degradation of the major iron transport molecule transferrin, whereas depletion of macrophages in mice increased transferrin levels in the duodenal villi. Inhibition of serine protease activity restored transferrin levels in the Tsc2-deficient mice. Physiologically, transferrin levels were regulated in the villi during Citrobacter rodentium infection in mice. These data show that transferrin is controlled locally in the duodenum and establish macrophages as regulators of duodenal iron uptake.
Project description:In the present study, we examined duodenal gene expression in rats subjected to immobilization, to elucidate the mechanism of the stress response in the duodenum. Keywords: stress response
Project description:The effect of iron-deficiency on duodenal gene expression was investigated in rats at different developmental stages. Keywords: time-course
Project description:In the present study, we examined duodenal gene expression in rats subjected to immobilization, to elucidate the mechanism of the stress response in the duodenum. Experiment Overall Design: Total RNA was extracted from the duodenal mucosa with an acid guanidinium thiocyanate-phenol-chloroform mixture. Total RNA was analyzed using the rat genome U34A microarray (Affymetrix). Gene intensity information was converted to a mean intensity for each gene using the manufacturerâs proprietary software (version 4.0; Affymetrix), which includes routines for data filtering and normalization.
Project description:Global transcriptional responses in duodenal intestinal epithelia of chickens following primary and secondary Eimeria acervulina infections.
Project description:Hypocalcemic vitamin D analogs are appealing molecules to exploit the immunomodulatory actions of active vitamin D in vivo. The functional modulation of dendritic cells is regarded as the key mechanism underlying their ability to regulate T cell responses. In contrast, the direct actions of vitamin D and structural analogs on T lymphocytes remain less well characterized. Microarray analysis was performed to gain insight into the direct immunomodulatory actions of TX527, a hypocalcemic vitamin D analog, on human T lymphocytes. Gene expression analysis revealed that TX527 regulated a wide variety of genes involved in different aspects of T cell function, including cellular growth and proliferation, cell death, cellular development, cellular movement and cell-to-cell signalling and interaction.
Project description:Vitamin D analogs alfacalcidol, paricalcitol, and VS-105 exhibit different effects on endothelial function and aortic gene expression in 5/6 NX uremic rats
Project description:Iron is an essential cellular trace element and important for many physiological functions including erythropoiesis and host defense. It is taken up from the diet in the duodenum, the first part of the small intestine by enterocytes and loaded onto transferrin, the main iron transport molecules in the circulation. Macrophages are ancient sentinel cells that are implicated in all steps of systemic iron metabolism except duodenal iron import. By assessing mice that harbor a macrophage-specific deletion of the tuberous sclerosis complex 2 (Tsc2), a negative regulator of mTORC1, we found that these mice possessed various defects in iron metabolism including defective steady state erythropoiesis and a highly reduced saturation of transferrin with iron. This iron-deficiency phenotype was caused by a block of iron import from the duodenal epithelial cells into the circulation. Activation of mTORC1 in villous duodenal CD68+ macrophages induced expression of serine proteases and promoted local degradation of the major iron transport molecule transferrin, whereas depletion of macrophages in mice increased transferrin levels in the duodenal villi. Inhibition of serine protease activity restored transferrin levels in the Tsc2-deficient mice. Physiologically, transferrin levels were regulated in the villi during Citrobacter rodentium infection in mice. These data show that transferrin is controlled locally in the duodenum and establish macrophages as regulators of duodenal iron uptake.
Project description:Vitamin D3 metabolites are capable of controlling gene expression in mammalian cells through two independent pathways: vitamin D receptor (VDR) and sterol regulatory element-binding protein (SREBP) pathways. In the present study, we dissect the complex biological activity of vitamin D by designing synthetic vitamin D3 analogs specific for VDR or SREBP pathway, i.e., a VDR activator that lacks SREBP inhibitory activity, or an SREBP inhibitor devoid of VDR activity.