TIMP-GLIA (gliadin nanoparticle) treatment in transgenic mice expressing celiac disease associated HLA-DQ8
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PROVIDER: PRJNA590711 | ENA |
REPOSITORIES: ENA
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Project description:This submission contains raw data obtained from RNA sequencing of mouse spleen cells. Spleen cells were derived from adult female HLA-DQ8, huCD4 transgenic Ab0 NOD mice, treated intravenously either with tolerogenic, immune-modifying nanoparticles containing gliadin (TIMP-GLIA), particles containing irrelevant control ovalbumin (TIMP-OVA), or not receiving treatment. Mice were then immunized with gliadin (except for negative controls), and spleens were collected after 28-30 days. Spleen cells were stimulated with gliadin (or controls) in culture for 72h, and RNA was obtained from cells for transcriptomic studies.
2019-11-21 | GSE140736 | GEO
Project description:Study of the effects of re-exposure to gliadin of intestinal biopsies from normalized celiac patients (>2 years on gluten free diet). Comparison of the expresson profile in biopsy portions incubated with 10ug/ml gliadin versus without gliadin for 4 hours.
2009-06-01 | E-MEXP-1823 | biostudies-arrayexpress
Project description:Background Celiac disease (CeD) is an autoimmune disorder triggered by gluten, with gliadin as the primary antigen. Therapies targeting gliadin to induce antigen-specific immune tolerance are of significant interest. This study investigates the therapeutic potential of a novel rapamycin-gliadin composite nanoparticle (PLN-GR) in enhancing Kupffer cell-mediated hepato-splenic dialogue to promote gluten tolerance in CeD. Methods Rapamycin-gliadin composite nanoparticles were synthesized using a precipitation self-assembly method and characterized for size, zeta potential, and cellular uptake. A CeD delayed-type hypersensitivity (DTH) mouse model was employed to evaluate the immunomodulatory effects of PLN-GR. Cellular biodistribution, immune phenotyping, and metabolic assessments were conducted to elucidate the nanoparticles' mechanism of action. Results Rapamycin-gliadin composite nanoparticles effectively targeted the liver and were internalized by Kupffer cells, inducing a tolerogenic phenotype. In vivo treatment with PLN-GR ameliorated systemic and intestinal inflammation in the CeD DTH mouse model, evidenced by reduced paw swelling and intestinal histopathology. The nanoparticles induced a metabolic shift from glycolysis to oxidative phosphorylation in macrophages, associated with increased itaconate production. This metabolic reprogramming was linked to an increase in PD-L1+ tolerogenic dendritic cells and a decrease in Th1 cell counts in the spleen. Conclusion The study demonstrates that rapamycin-gliadin nanoparticles can induce antigen-specific tolerance in CeD by modulating hepatic and splenic immune responses. The findings suggest a potential therapeutic strategy for CeD by enhancing immunometabolic reprogramming and inter-organ communication.
2025-07-30 | GSE275197 | GEO
Project description:Study on the effects of long term, dietary, consumption of gliadin (gluten) in patients with celiac disease. Comparison of expression profiles of biopsies from normalized patients treated with gluten-free diet >2 years (FU-follow-up samples) versus biopsies from patients with active disease (Dx-at diagnosis samples)
2009-06-01 | E-MEXP-1828 | biostudies-arrayexpress
Project description:TIMP-2 is an endogenous angiogenesis inhibitor, i.e. inhibits endothelial cell proliferation and tumor angiogenesis. As a result, TIMP-2 inhibits tumor growth and progression to metastasis. Understanding, therefore, the mechanisms of TIMP-2-mediated tumor growth inhibition would provide further support on the use of TIMP-2 as a novel biological agent for cancer therapy. We used microarray analysis to determine the TIMP-2 and Ala+TIMP-2 transcriptional profiles of A549 cancer cells in order to understand how TIMP-2 inhibits tumor growth and angiogenesis.
2013-01-28 | GSE38408 | GEO
Project description:TIMP-2 is an endogenous angiogenesis inhibitor, i.e. inhibits endothelial cell proliferation and tumor angiogenesis. As a result, TIMP-2 inhibits tumor growth and progression to metastasis. Understanding, therefore, the mechanisms of TIMP-2-mediated tumor growth inhibition would provide further support on the use of TIMP-2 as a novel biological agent for cancer therapy. We used microarray analysis to determine the TIMP-2 and Ala+TIMP-2 transcriptional profiles of A549 cancer cells in order to understand how TIMP-2 inhibits tumor growth and angiogenesis. We overexpressed TIMP-2 and its mutant (does not inhibit MMP) in A549 human lung cancer cells and determined TIMP-2 and Ala+TIMP-2 transcriptional profiles, groups of genes and associated biological functions. We then injected the cells in NOD-SCID mice and RNA from tumors were isolated for further analysis to identify genes that are associated with tumor growth inhibition.
2013-01-28 | E-GEOD-38408 | biostudies-arrayexpress
Project description:Celiac disease (CeD) is an immune-mediated chronic enteropathy caused by gluten exposure in HLA-DQ2 and/or -DQ8 positive individuals. The hallmarks of CeD include increased intraepithelial lymphocytes and villous atrophy. Clinically, a small subset of individuals with elevated serum tissue transglutaminase antibody (TTG) concentrations but unremarkable duodenal mucosa at initial endoscopy may progress to CeD over time. We hypothesize that these rare CeD precursor cases can allow us to interrogate histologic and molecular signatures to predict those who subsequently develop CeD, and to study the final cascade into overt lesions in CeD.
2025-08-06 | GSE273155 | GEO
Project description:FASTBAC-Seq of the timP toxin mRNA to identify loss-of-function mutations. We selected and deep-sequenced surviving transformants expressing mutagenized timP under the J23106 promoter and performed differential expression analysis (compared to a strain not expressing timP = NP) to identify enriched single-nucleotide substitutions. The timP locus originates from S. enterica Typhimurium strain SL1344 (TA07144 from T1TAdb database).
2026-03-05 | GSE313366 | GEO
Project description:We collected 19 duodenal biopsies of children and adults with celiac disease and compared the expression of 38 selected genes between each other and with the observed in 13 non-celiac disease controls matched by age. qPCR gene expression profiling. Intestinal samples from children and adults with active celiac disease patients and controls were analysed.
2015-12-19 | E-GEOD-76168 | biostudies-arrayexpress
Project description:Gemcitabine constitutes one of the backbones for chemotherapy treatment in pancreatic ductal adenocarcinoma (PDAC) but patients often show poor or complete lack of response to this agent. Molecular markers downstream of Gemcitabine treatment in pre-clinical models may provide an insight into resistance mechanisms. We identified potential secretory biomarkers of Gemcitabine resistance (response) in the transgenic KRasG12D; Trp53R172H; Pdx-1 Cre (KPC) mouse model of PDAC using cytokine arrays. We validated the oncogenic role of the cytokine tissue inhibitor of matrix metalloproteinases 1 (TIMP-1) in primary pancreatic tumours and metastasis using both in vitro techniques and animal models. We identified potential pathways affected downstream of TIMP-1 using the Illumina Human H12 array. Our findings were validated in both primary and metastatic models of pancreatic cancer. Gemcitabine increases inflammatory cytokines including TIMP-1 in the KPC mouse model. TIMP-1 is upregulated in patients with pancreatic intraepithelial neoplasias grade 3 and PDAC lesions relative to matched normal pancreatic tissue. Additionally, we demonstrate that TIMP-1 plays a role in tumour proliferation and angiogenesis, while inhibition resensitises to gemcitabine and radiotherapy. Strikingly, serum TIMP-1 levels support the formation of liver metastasis through the recruitment of immunosuppressive cell populations, such as CD11b+Gr1+ myeloid cells and CD4+CD25+FOXP3+ Tregs to the hepatic microenvironment. Gemcitabine treatment results in upregulation of the pro-tumourigenic/pro-metastatic cytokine TIMP-1, which partially explains the therapeutic resistance and poor responses to this therapy in PDAC. Our study provides a rationale for the development and testing of TIMP-1 specific inhibitors in addition to chemo/radiotherapy.
2017-08-08 | GSE94891 | GEO