Different response of WT and Ts keratinocyte to TPA treatment
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Annan Yang
PROVIDER: E-GEOD-40382 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Ts keratinocyte has increased proliferation compare to WT keratinocyte upon TPA treatment. This result showed the different transcription regulation in Ts and WT keratinocyte upon TPA treatment.
2013-06-01 | GSE40382 | GEO
Project description:Cutaneous squamous tumors rely on autocrine/paracrine loops for proper fitness. Targeting this Achilles’ heel is therefore considered a potential avenue for patient treatment. However, the mechanisms that engage and sustain such programs during tumor ontogeny are poorly understood. Here, we show that two Rho/Rac activators, the exchange factors Vav2 and Vav3, control the expression of an epithelial autocrine/paracrine program that regulates keratinocyte survival and proliferation as well as the creation of an inflammatory microenvironment. Vav proteins are also critically involved in some of the subsequent autocrine signaling loops activated in keratinocytes. The genetic inactivation of both Vav proteins reduces tumor multiplicity without hampering skin homeostasis, thus suggesting that pan-specific Vav therapies may be useful in skin tumor prevention and treatment. The dorsal skin of WT and DKO mice (Vav2-/-;Vav3-/-) were treated with either one or four applications of phorbol ester 12-O-tetradecanoylphorbol-13 acetate (TPA) (6.8 nmol in 200 μl acetone) two days after shaving. As control, we applied 200 μl of acetone. Animals were euthanized 24 hours after treatment.
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Project description:Human primary keratinocytes were left untreated or treated for 48 hr with 12-O-tetradecanoylphorbol-13-acetate (TPA) and expression profiles were compared to find long ncRNAs expressed and differentially regulated upon differentiation. 4 replicates of minus TPA and 3 of plus TPA with dye-swap. Custom-made microarray from Agilent.
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Project description:This experiment was designed to determine if deletion of the dual-specificity MAP kinase phosphatase encoded by DUSP5 had any effect on the pattern of gene expression in cells treated with the phorbol ester tumour promoter TPA. Sex matched primary WT and DUSP5 knockout MEFs were isolated from littermate embryos and cultured. Cells were then exposed to TPA for 0, 1 and 3h before isolation of RNA prior to microarray hybrdisation and data analysis. Our results show that the transcript levels of a subset of TPA-inducible genes are altered in cells that lack DUSP5. Primary sex-matched wild type (WT) and DUSP5 knockout (KO) mouse embryonic fibroblasts (MEFs) were derived from littermate day 13.5 embryos. Cells were treated for 0, 1 and 3 hours with TPA, and the experiment was done in triplicate (18 samples in total).
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Project description:Analysis of differential gene expression during TPA-induced megakaryocyte differentiation of human erythroleukemia K562 cells. The transcription profile of untreated vs TPA-treated K562 cells for 2 days was compared using gene microarrays.
2009-09-01 | E-MEXP-2213 | biostudies-arrayexpress
Project description:The goal of this study is to compare gene expression differences between WT and tPA KO mice 4 weeks after overexpression of human alpha-synuclein in the substantia nigra
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Project description:Inducible keratinocyte-specific ILEI overexpression in mice (K5-ILEIind) recapitulates many aspects of psoriasis following TPA challenge, primarily manifested by impaired epidermal differentiation and increased neutrophil recruitment. Mechanistically, ILEI triggers Erk and Akt signaling, which then activate STAT3 via Ser727 phosphorylation. Keratinocyte-specific ILEI deletion ameliorates TPA-induced skin inflammation. A transcriptomic ILEI signature obtained from the K5-ILEIind model shows enrichment in several signaling pathways also found in psoriasis and identifies urokinase as a targetable enzyme to counteract ILEI activity. Pharmacological inhibition of urokinase in TPA-induced K5-ILEIind mice results in significant improvement of psoriasiform symptoms by reducing ILEI secretion. The ILEI signature distinguishes psoriasis from healthy skin with uPA ranking among the top “separator” genes. Our study identifies ILEI as a key driver in psoriasis, indicates the relevance of ILEI-regulated genes for disease manifestation and shows the clinical impact of ILEI and urokinase as novel potential therapeutic targets in psoriasis.
2023-04-12 | E-MTAB-12849 | biostudies-arrayexpress
Project description:The chemokine decoy receptor D6 internalises and degrades inflammatory CC chemokines enabling resolution of inflammation. In D6 deficient mice (D6 KO), otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study we have used transcriptomic approaches to define the molecular make up of this response. The result of such analysis highlights potential roles for a number of cytokines iniating and maintaining psoriasis like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology Backskin of D6 null mice was painted with three successive applications of 50uM TPA (in acetone), 24 hours apart. Control (labelled as day 0 or untreated) were treated with acetone only. After the three successive applications of TPA, pathology was left to develop for 1, 2, 4 or 6 days and backskin was taken for microarray analysis at each of these time points. To identify differentially expressed genes, comparisons were made between D6 KO and WT mice at each time point (D6 KO vs WT mice at day 0, day 1, day 2, day 4 or day 6). Significantly differentially expressed genes (p<0.05 according to an unpaired t-test) and up or down regulated more than 3 fold were identified ay each time point and selected for further analysis.
2013-05-28 | E-GEOD-46889 | biostudies-arrayexpress
Project description:Embryonic stem (ES) cells and embryos reversibly pause via chemical mTOR inhibition. In this study, we investigate the tissue-specific response to mTORi-induced pausing in ES and trophoblast stem (TS) cells. To resolve the sequential rewiring of the proteome, we conducted a time-series proteomics experiment at 1, 3, 6, 12, 24, and 48 hours upon induction of pausing, and at 1, 3, 6, 12, 24, and 48 hours upon release of pausing in ES and TS cells. We find that ES, but not TS cells pause reversibly. To optimise developmental pausing conditions, we reasoned that by understanding the difference in pausing response of ES and TS cells, we could identify which pathways are essential for pausing. We found that KEGG pathways related to amino acid degradation, fatty acid degradation, and DNA repair are upregulated in ES cells, but downregulated in TS cells during entry into pausing. Moreover, by targeted metabolomics, we found a depletion of short chain carnitines in the paused ES cells. To extend the length of developmental pausing, we supplemented paused embryos with L-carnitine. The L-carnitine supplementation facilitates lipid usage and prolongs the pausing length by 19 days through the establishment of a more dormant state.
2023-11-06 | PXD033798 | Pride
Project description:Seroepidemiological studies imply a correlation between Epstein-Barr virus (EBV) reactivation and the development of nasopharyngeal carcinoma (NPC). Phorbol esters, butyrates and N-nitroso compounds are known chemical carcinogens in foodstuffs and cigarettes that have been implicated as risk factors contributing to the development of NPC. We have demonstrated previously that low dose N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 0.1 microg/ml) had a synergistic effect with 12-O-tetradecanoylphorbol-13-acetate (TPA) and sodium butyrate (SB) in enhancing EBV reactivation (Chem Biol Interact 188: 623-634). Since residents of areas with a high risk of NPC are reported to contact with these carcinogens (TPA, SB or nitrosamines) frequently, we sought to determine the consequence of repeated exposure of EBV-harboring nasopharyngeal cells to these carcinogens in a long-term, low dose, repeated manner. An NPC cell line latently infected with EBV, NA, was periodically treated with TPA/SB combined with MNNG for recurrent EBV reactivation. After 10 times of chemically-induced recurrent reactivation of EBV, the expression profile analysis indicates that many carcinogenesis-related genes were altered in recurrent reactivated NA cells when compared to the parental NA cells. The expression profile was analyzed in the recurrent EBV reactivated NA cells and the parental NA cells. The expression profile of two NA cells, NA-P10/TS-MG and NA-P1/mock, were analyzed in this study. NA-P10/TS-MG cells were subject to 10 times of repeated chemical exposure by incubating these cells periodically with TPA/SB (10 ng/ml and 1.0 mM) in combination with MNNG (0.1 microg/ml). The NA cells at the beginning of this experiment were defined as passage 0 (P0) cells. 24 h after seeding, the cells were subjected to a 24 h period of mock or chemical treatment. After this 24 hr treatment, the cells were recovered by replacing the medium with fresh (treatment-free) medium and incubation for a further 48 h. The resulting cells were defined as passage 1 (P1) cells. Cells from P1 were trypsinized and transferred and the process repeated again to obtain the P2 cells. A total of ten treatments were applied to the cells in this study. M-bM-^@M-^\NA-P10/TS-MGM-bM-^@M-^] refers to NA cells with 10 times of combined TPA/SB and MNNG (TS-MG) treatments. NA-P1/mock is mock-treated NA cells with one time of passage that was used as reference in this study. Replicates were included for each samples.
2012-08-14 | E-GEOD-38453 | biostudies-arrayexpress