Project description:Primary aldosteronism (PA) is the most frequent form of secondary arterial hypertension. Mutations in different genes increase aldosterone production in PA, but additional mechanisms may contribute to increased cell proliferation and aldosterone producing adenoma (APA) development. We performed transcriptome analysis in APA and identified retinoic acid receptor alpha (RARα) signaling as a central molecular network involved in nodule formation. To understand how RARα modulates adrenal structure and function, we explored the adrenal phenotype of male and female Rarα knockout mice. Inactivation of Rarα in mice led to major structural disorganization of the adrenal cortex in both sexes, with increased adrenal cortex size in female mice and increased cell proliferation in males. Abnormalities of vessel architecture and extracellular matrix were due to decreased Vegfa expression and modifications in extracellular matrix components. On the molecular level, Rarα inactivation leads to inhibition of non-canonical Wnt signaling, without affecting the canonical Wnt pathway nor PKA signaling. Our study suggests that Rarα contributes to the maintenance of normal adrenal cortex structure and cell proliferation, by modulating Wnt signaling. Dysregulation of this interaction may contribute to abnormal cell proliferation, creating a propitious environment for the emergence of specific driver mutations in PA.
Project description:A study of rat femoral fracture healing in young (6 weeks old at fracture), adult (26 weeks old at fracture), and old (52 weeks old at fracture) rats. Samples were collected at time of surgery (intact controls) and at 3 days, 1 week, 2 weeks, 4 weeks, and 6 weeks after fracture. Samples were the mid third of the femoral length including the external callus, cortical bone and marrow elements. Fracture was stabilized with an intramedullary rod prior to fracture with a Bonnarens and Einhorn device.
Project description:Comparison between ChIP-Seq data of RAR? and RAR?, between RAR and RXR, as well as between control and retinoic acid-treatment for each investigated nuclear receptors. Mouse were treated by control diet and RA-diet for 1 days. After treatment, livers were used to do ChIP using antibodies of RXR?, RAR?, and RAR?. An aliquote of total chromatin without pull-down process by any antibodies was used as input control. A single-end read of 35bp sequencing was performed on each of ChIPed DNA and input. Sequencing data of RAR? and RAR? were compared to each other. In addtional, each of RAR? and RAR? data were compared with RXR? data. For each nuclear receptor, ChIP-Seq data prior or after RA-treatment were also compared with each other.
Project description:Bone endothelial cells (ECs) were purified from male and female mice of 2 weeks and 65 weeks old. RNA sequencing was performed to understand sex- dependent gene expression pattern in bone ECs during development and ageing to understand blood vesssel role in sex differences observed in bones. Further comparison of young and old mice would beneficial in understanding sex specific ageing mechanism.
Project description:Bone endothelial cells (ECs) were purified from male and female mice of 12 weeks old. RNA sequencing was performed to understand sex- dependent gene expression pattern in bone ECs during development and ageing to understand blood vesssel role in sex differences observed in bones. Further comparison of young and old mice would beneficial in understanding sex specific ageing mechanism.
Project description:This study investigates the effects of the aryl hydrocarbon receptor (AhR) ligands TCDD and PCB126 on hepatic gene expression in female sprague dawley rats. Rats were treated with toxicological equivalent doses of TCDD (100ng/kg/day) (Toxic equivalence factor (TEF) = 1.0), PCB126 (30ng, 300ng or 1000ng/kg/day) (TEF = 0.1) or a vehicle control of corn oil:acetone (99:1) 5 days a week for 52 weeks.
Project description:To investigate the effects of gene Fmod on affecting brain dysfunction and metabolic disorders by profiling the transcripome in the hypothalamus and liver of male Fmod_KO mice at 13 weeks old.