Project description:T cells undergo autoimmunization following spinal cord injury (SCI) and play both protective and destructive roles during the recovery process. T-cell deficient athymic nude (AN) rats recover better than immunocompetent Sprague-Dawley (SD) rats following spinal cord transection. In the present study, we evaluated locomotor recovery in SD and AN rats following moderate spinal cord contusion. To explain variable locomotor outcome, we assessed whole-genome expression using RNA sequencing, in the acute (1 week post-injury) and chronic (8 weeks post-injury) phases of recovery. AN rats demonstrated greater locomotor function than SD rats only at 1 week post-injury, coinciding with peak T cell infiltration in immunocompetent rats. Genetic markers for T cells and helper T cells were acutely enriched in SD rats, while AN rats expressed genes for Th2 cells, cytotoxic T cells, NK cells, mast cells, IL-1a, and IL-6 at higher levels. Acute enrichment of cell death-related genes suggested that SD rats undergo secondary tissue damage from T cells. Additionally, SD rats exhibited increased acute expression of voltage-gated potassium (Kv) channel-related genes. However, AN rats demonstrated greater chronic expression of cell death-associated genes and less expression of axon-related genes. We put forth a model in which T cells facilitate early tissue damage, demyelination, and Kv channel dysregulation in SD rats following contusion SCI. However, compensatory features of the immune response in AN rats cause delayed tissue death and limit long-term recovery. T cell inhibition combined with other neuroprotective treatment may thus be a promising therapeutic avenue. 2x2 model with 4 groups and 12 total samples. 2 rat strains (athymic nude [AN] and Sprague-Dawley [SD]) and 2 time points (1 week post-injury [acute] and 8 weeks post-injury [chronic]). 3 samples per group, for a total of 12 samples. No technical replicates were performed. Acute SD group = rats 618, 619, and 620. Chronic SD group = rats 605, 606, and 608. Acute AN group = rats 714, 715, and 717. Chronic AN group = rats 707, 712, and 713.
Project description:This study identifies molecular changes in hematopoietic stem cells (HSC) isolated from mice with chronic autoimmune arthritis induced using the collagen-induced arthritis (CIA) model.
Project description:Intraperitoneal injection of tremolite initiates mesothelial injury and chronic inflammation that causes the development of malignant mesothelioma (MM). We performed high-resolution comparative genomic hybridization to identify characteristics in the genomic profiles of tremolite-induced MMs in rats.
Project description:To determine te lncRNA expression profile in collagen-induced arthritis rats and normal rats, we uesed lncRNA microArray analysis form Arraystar to examine the expression of lncRNAs in CIA and normal rats' synovial tissues.
Project description:We used microarrays to detail transcriptional changes in cultured human smooth muscle cells in response to acute and chronic 2-methoxyestradiol treatment 2-ME, an endogenous metabolite. of estradiol, not only exerts cytotoxic effects on cancer cells but it also protects against multiple proliferative disorders, including atherosclerosis and injury-induced intimal thickening Keywords: treatment vs. control Human aortic smooth muscle cells cultures with/without 2-methoxyestradiol (acute/chronic treatment)
Project description:Investigating acute exercise response over time in mice and rats Gene expression profiling of mice and rats (different training status), 1 hour after an acute exercise bout.
Project description:Hepatic fibrosis, the wound-healing response to repeated liver injury, ultimately leads to cirrhosis. There is an urgent need to develop effective antifibrotic therapies. Ghrelin (encoded by Ghrl) is an orexigenic hormone that has pleiotrophic functions including protection against cell death1. Here we investigate whether ghrelin modulates liver fibrosis and protects from acute liver injury. Recombinant ghrelin reduced the fibrogenic response to prolonged bile duct ligation in rats. This effect was associated with decreased liver injury and myofibroblast accumulation as well as attenuation of the altered gene expression profile. Ghrelin also reduced fibrogenic properties in cultured hepatic stellate cells. Moreover, Ghrl-/- mice developed exacerbated hepatic fibrosis and liver damage after chronic injury. Ghrelin also protected rat livers from acute liver injury and reduced the extent of oxidative stress and the inflammatory response. In patients with chronic liver diseases, ghrelin serum levels decreased in those with advanced fibrosis and hepatic expression of the ghrelin gene correlated with expression of fibrogenic genes. Finally, in patients with chronic hepatitis C, single nucleotide polymorphisms of the ghrelin gene (-994CT and â604GA) influenced the progression of liver fibrosis. We conclude that ghrelin exerts antifibrotic effects on the liver and may represent a novel antifibrotic therapy. Experiment Overall Design: Rats were divided into three groups: control rats receiving saline (sham operation), rats with bile duct ligation receiving saline and rats with bile duct ligation receiving recombinant ghrelin (10 micrograms/Kg/day by a subcutaneous osmotic mimi-pump). For the microarray analysis samples from 6 rats were analyzed except for the ghrelin-treated group (5 rats).
Project description:Antibiotic-refractory Lyme arthritis (ARLA) is defined by persistent arthritis after sufficient antibiotic treatment of acute Lyme arthritis and is seen in approximately 10 % of patients with Lyme arthritis. Although some clinical and genetic risk markers for ARLA have been elucidated, whether chronic inflammation is sustained by persistent Borrelial antigens or triggered by autoantigens is not elucidated yet. Here, we show an oligoclonal expansion of peripheral T helper (TPH) cells in synovial fluid (SF) of pediatric ARLA patients. By in-depth bioinformatics analysis we identify a group of T cell receptors (TCRs) in this cell population shared between ARLA patients with a HLA-DRB1*11 background. By delineating surrogate markers for this convergent T cell response, we can show that these TCRs are specific for ARLA patients with HLA-DRB1*11 background compared to different autoimmune and infectious causes of arthritis and that those markers persist throughout disease course. Furthermore, combined single cell transcriptome and paired TCRα/β sequencing links the ARLA specific surrogate markers to cells with an inflammatory transcriptional program driven by TCR signaling – revealing possible therapeutic targets. Concluding, this study reveals an HLA-DRB1 restricted convergent TPH cell response in the joints of pediatric ARLA patients – suggesting a common persisting antigen as causative agent.