RNA-seq of C3H/HeJ AA mice skin biopsies treated with JAK-selective inhibitors
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE167360 | GEO | 2021/02/24
REPOSITORIES: GEO
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Project description:Our goal was to identify gene expression patterns that correlated with treatment of established autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation skin from 3 mice were taken at 6, 12 and, in some cases, 24 weeks of topical drug administration following grafting; mice were treated with ruxolitinib (jak1i), tofacitinib (jak3i), or control pbs 3 biological replicates were taken at each time point for each treatment modality
2014-08-17 | E-GEOD-45514 | biostudies-arrayexpress
Project description:Our goal was to identify gene expression patterns that correlated with treatment of established autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation skin from 3 mice were taken at 6, 12 and, in some cases, 24 weeks of topical drug administration following grafting; mice were treated with ruxolitinib (jak1i), tofacitinib (jak3i), or control pbs
2014-08-17 | GSE45514 | GEO
Project description:Our goal was to develop a transcriptomic description of affected alopecic skin from aged C3H/HeJ mice. Affected skin from 3 mice was compared to skin from similarly aged but unaffected C3H/HeJ mice.
2014-08-17 | GSE45513 | GEO
Project description:The myeloma bone marrow microenvironment drives proliferation of malignant plasma cells and promotes resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells.Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not rescue ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells drive a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.
2018-10-24 | PXD006581 | Pride
Project description:Our goal was to identify gene expression patterns that correlated with prevention of autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation skin from 3-5 mice were taken at 5/6 weeks and 12/13 weeks of drug administration following grafting; mice were treated with ruxolitinib (jak12i) by oral gavage, tofacitinib (jak3i) by osmotic pump, antiIL15R-beta antibody by i.p. injection, or control pbs by either ip injection, oral gavage, or osmotic pump. sham indicates mice that received no graft. 3-5 biological replicates were taken at each time point for each treatment modality
2014-08-17 | E-GEOD-45551 | biostudies-arrayexpress
Project description:Our goal was to develop a transcriptomic description of affected alopecic skin from aged C3H/HeJ mice. Affected skin from 3 mice was compared to skin from similarly aged but unaffected C3H/HeJ mice. 3 biological replicates from 3 separate affected mice compared with 3 biological replicate controls from 3 unaffected mice
2014-08-17 | E-GEOD-45513 | biostudies-arrayexpress
Project description:We previously reported that JAK/STAT pathway-mediated regulation of IRF-related genes may have an important role in the disease activity of SLE through analyzing the difference of gene expression in peripheral blood CD3+ T cells obtained from SLE patients. Recently pan-JAK inhibitor (JAKi) tofacitinib (TOFA) were developed and successfully applied to patients with rheumatoid arthritis. Therefore, the application possibility of TOFA was investigated for the new therapeutic strategy of SLE. Anti-dsDNA antibody and proteinuria were decreased and glomerulo/interstitial nephritis were ameliorated in any TOFA administered SLE mice. In splenic CD4+ T cell analysis, naïve cells significantly increased and effector/memory cells decreased. TOFA with dexamethasone (DEXA) therapy showed tendency to indicate stronger inhibitory effect comparing with TOFA or DEXA monotherapy. The gene expression of Ifit3/IFIT3 that related with anti-viral IFN signaling pathway was significantly suppressed in both CD4+ from SLE mice and CD3+ T cells from SLE patients after treatment. Both TOFA monotherapy and dual therapy with DEXA could suppress nephritis and modify immunological function in SLE mice with different genetic background. IFN signaling pathway was supposed to be important for the functional mechanism of TOFA to improve the disease condition. TOFA may contribute to the development of a new therapeutic strategy for SLE. The gene expression analysis was compared among tofacitinib, tofacitinib+dexamethsone, dexamethsone and non-treated control groups and extracted TOFA specific decreased genes in NZBWF1 mice.
2016-03-03 | E-GEOD-78825 | biostudies-arrayexpress
Project description:Transformation of post-myeloproliferative neoplasms into secondary (s) AML exhibit poor clinical outcome. In addition to increased JAK-STAT and PI3K-AKT signaling, post-MPN sAML blast progenitor cells (BPCs) demonstrate increased nuclear β-catenin levels and TCF7L2 (TCF4) transcriptional activity. Knockdown of β-catenin or treatment with BC2059 that disrupts binding of β-catenin to TBL1X (TBL1) depleted nuclear β-catenin levels. This induced apoptosis of not only JAKi-sensitive but also JAKi-persister/resistant post-MPN sAML BPCs, associated with attenuation of TCF4 transcriptional targets MYC, BCL-2 and Survivin. Co-targeting of β-catenin and JAK1/2 inhibitor ruxolitinib (rux) synergistically induced lethality in post-MPN sAML BPCs and improved survival of mice engrafted with human sAML BPCs. Notably, co-treatment with BET protein degrader ARV-771 and BC2059 also synergistically induced apoptosis and improved survival of mice engrafted with JAKi-sensitive or JAKi-persister/resistant post-MPN sAML cells. These preclinical findings highlight potentially promising anti-post-MPN sAML activity of combination of β-catenin and BETP antagonists against post-MPN sAML BPCs.
2021-09-20 | GSE120639 | GEO
Project description:Our goal was to identify gene expression patterns that correlated with prevention of autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation skin from 3-5 mice were taken at 5/6 weeks and 12/13 weeks of drug administration following grafting; mice were treated with ruxolitinib (jak12i) by oral gavage, tofacitinib (jak3i) by osmotic pump, antiIL15R-beta antibody by i.p. injection, or control pbs by either ip injection, oral gavage, or osmotic pump. sham indicates mice that received no graft.
2014-08-17 | GSE45551 | GEO
Project description: Not available
| S-EPMC4262666 | biostudies-literature