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GSE101508
Homo sapiens
10 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Cardiovascular diseases (CVD), including atherosclerosis, are globally the leading cause of death. Key factors contributing to onset and progression of atherosclerosis and plaque development include the pro-infslammatory cytokines Interferon (IFN) and IFN and the Pattern Recognition Receptor (PRR) Toll-like receptor 4 (TLR4). Together, they trigger activation of members of the Signal Transducer and Activator of Transcription (STAT) family. Searches for STAT3-targeting compounds, exploring the pTyr-SH2 interaction area of STAT3, yielded many small molecules, including STATTIC and STX-0119. However, many of these inhibitors do not seem STAT-specific. We hypothesized that non-specific STAT-inhibitors that simultaneously block STAT1, STAT2 and STAT3 activity and pro-inflammatory target gene expression may be a promising avenue for the treatment of CVD. We developed a pipeline approach combining comparative in silico docking of multiple STAT-SH2 models on multi-million Clean Lead and Clean Drug-Like libraries with in vitro STAT inhibition validation, as a novel STAT-inhibitory selection strategy. This approach allowed us to identify a new type of non-specific STAT inhibitor, C01L_F03 targeting the SH2 domain of STAT1, 2 and 3 with equal affinity. Moreover we observed a similar STAT cross-binding mechanism for STATTIC and STX-0119, leading to genome-wide inhibition of pro-atherogenic gene expression. Consequently, a multi-STAT inhibitory strategy was applied to inhibit endothelial cell (EC) migration, leukocyte adhesion to ECs and impairment of aortic ring contractility under inflammatory conditions. Together, this implicates that multi-STAT inhibition could provide a powerfull approach for the success of combating vascular inflammation in CVD
Publication Title
No associated publication
Sample Metadata Fields
Cell line, Treatment
View Samples- Populus trichocarpa
- 18 Downloadable Samples
- Affymetrix Poplar Genome Array (poplar)
Description
We studied the changes that occur in gene transcription during seasonal senescence in Populus trichocarpa pioneer leaves and fine roots. Plant senescence is a strictly regulated physiological process that allows relocating of valuable nutrients from senescent tissues before death. It might be induced by internal or external factors and among them, phytohormones play an undoubtedly significant role. Senescence was extensively studied in leaves, but the aging of other ephemeral organs, located underground, and its drivers are still poorly understood. We focused on collective results to fill in the knowledge gap about senescence of fine, absorptive roots and leaves in order to check if there are universal mechanisms involved during plant organ senescence. Transcriptional profiling was conducted with the use of microarrays to identify genes involved in developmental PCD. Samples were collected three times during a growth season. The first collection was considered as a control and was collected in early summer (July 7–15) when leaves and the root system were fully developed and functional. The second group of leaf and root samples were harvested in early autumn (October 1–7) when chlorophyll levels in leaves had decreased by approximately 40% and when fine roots had changed in color from white to brown. The third group of samples were harvested in the middle of autumn (November 2–9) when chlorophyll levels in leaves decreased by approximately 65% and fine roots were dark brown or black color. Our results reveal the important role of phytohormones in regulating the senescence of both studied organs. The transcriptomic analyses showed significant changes in gene expression that are associated with phytohormones, especially with ABA and jasmonates. We conclude that phytohormonal regulation of senescence in roots and leaves is organ-specific. In roots, phytohormones are involved indirectly in regulation of senescence by increasing tolerance for cold or resistance for pathogens, whereas such correlation was not observed in leaves.
Publication Title
Allies or Enemies: The Role of Reactive Oxygen Species in Developmental Processes of Black Cottonwood (<i>Populus trichocarpa</i>).
Sample Metadata Fields
Specimen part
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