Gene expression profile associated with the PDZ ligand-motif of HPV16-E6 oncoprotin in the skin of transgenic mice models
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Laura Uribe
PROVIDER: E-GEOD-22417 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The HPV16-E7 oncoprotein and 17β-estradiol are import factors for the induction of premalignant lesions and cervical cancer. The study of these factors is crucial for a better understanding of cervical tumorigenesis. In this study, we performed a microarray analysis to obtain a global gene expression profile induced by both, HPV16-E7 and 17β-estradiol in cervical tissue of K14E7 transgenic mice. We found that 17β-estradiol is the main cause of the up-regulation of a large number of cellular genes involved in the immune response whereas E7 oncoprotein mainly affects the cellular metabolism. Our microarray data also shows some novel differentially expressed genes that were not previously reported in cervical cancer. The identification of these genes, regulated by E7 and 17β-estradiol, provides the basis for further studies on their role in cervical carcinogenesis. 15 Mouse Gene 1.0 ST Affymetrix microarrays were used to analyze gene expression of cervical tissue from K14E7 hemizygote and nontransgenic FvB control virgin female untreated and treated mice. Briefly, one-month virgin female transgenic and nontransgenic mice were implanted in the dorsal skin with continuous release pellets delivering 0.05 mg of17-β estradiol over 60 days. As control samples we used K14E7 and FvB untreated mice. For the microarray analysis we used triplicates for each group (3 treated K14E7 mice, 3 treated FvB mice, 3 untreated K14E7 mice, 3 untreated FvB mice).
2013-07-01 | E-GEOD-46890 | biostudies-arrayexpress
Project description:The K14E6 transgenic mice developskin hyperplasia,benign tumors and skin cancer. The tumor formation capacity diminishes when E6 lacks its PDZ ligand-motif. This study aims to compare the transciptional profiles of transgenic K14E6 mice with K14E6 Δ146-151 (lacking the PDZ domain) in order to explore the role of PDZ in early skin carcinogenesis.
2010-07-27 | GSE22417 | GEO
Project description:The K14E6 transgenic mice develop skin hyperplasia, benign tumors, and cancer in the dorsal skin spontaneously. The E6 oncoprotein own its tumorigenic potential to a region located near the C-Terminal domain, better known as the PDZ ligand-domain. The aim of this work was to describe early cellular processes affected by the E6’s PDZ ligand-domain when is expressed in the skin of transgenic mice using microarray technology. Results. A total of 222 genes were differentially expressed (FC:1.5, Adj.p.value <0.05, and b value > 0.5) in the skin of K14E6 mice as compared to K14E6Δ146-151 mice. Out of those, 70 genes were up-regulated and 151 genes were down-regulated. Enzyme linked receptor protein signaling was the most affected process in our data, followed by cell adhesion, development, and lipid biosynthesis. We also found that the K14E6 strains induces the mRNA of the wound-inducible gene K6b, and delocalizes E-cadherin protein in the entire epidermis. Finally, CD34 and K15 epidermal stem cell marker proteins diminish its expression in the skin, in a PDZ-dependent manner. Conclusions. The PDZ ligand-domain of HPV16-E6 oncoprotein affects the expression of several genes involved in cellular processes that could be relevant in the HPV-induced carcinogenesis. Since HPV16-E6 oncoproteins lacking the PDZ ligand-domain loose its oncogenic potential, the knowledge of genes transcriptionally affected by the E6’s PDZ ligand-domain will provide valuable information about HPV-induced skin carcinogenesis.
2017-11-30 | GSE99868 | GEO
Project description:Herein we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n=3) were compared with littermate controls (n=3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average P = 0.0082; cystatin A, human orthologue); slc25a5 (average fold change of 46.2 and an average P = 0.0318); serpinb3b (average fold change of 35.6 and an average P = 0.0345; serpinB1, human orthologue); and kallikrein related peptidase 6 (average fold change of 4.7 and an average P = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, P < 0.0001), KLK6 (9.0-fold, P = 0.002), stefin A1 (7.3-fold; P < 0.001) and slc25A5 (1.5-fold; P = 0.05) using qRT-PCR on a second cohort of animals (n=8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; P < 0.05), 29,000-fold (stefinA1; P < 0.01), 322-fold (KLK6; P < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes vs. healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3.0-fold), KLK6 (5.8-fold) and serpinB1 (76-fold; all P < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover slc25a5, cystatin A, KLK6 and serpinB1 protein were all increased in lesional psoriasis skin compared to normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.
2014-10-30 | PXD001387 | Pride
Project description:The environment outside the Earth’s protective magnetosphere is a much more threatening and complex space environment. The dominant causes for radiation exposure, solar particle events and galactic cosmic rays, contain high-energy protons. In space, astronauts need healthy and highly functioning cognitive abilities, of which the hippocampus plays a key role. Therefore, understanding the effects of 1H exposure on hippocampal-dependent cognition is vital for de-veloping mitigative strategies and protective countermeasures for future missions. To investi-gate these effects, we subjected 6-month-old female CD1 mice to 0.75 Gy fractionated 1H (250 MeV) whole-body irradiation at the NASA Space Radiation Laboratory. The cognitive perfor-mance of the mice was tested 3 months after irradiation using Y-maze and morris water maze tests. Both sham-irradiated and 1H-irradiated mice significantly preferred exploration of the novel arm compared to the familiar and start arms, indicating intact spatial and short-term memory. Both groups statistically spent more time in the target quadrant, indicating spatial memory retention. There were no significant differences in neurogenic and gliogenic cell counts after irradiation. In addition, proteomic analysis revealed no significant upregulation or down-regulation of proteins related to behavior, neurological disease, or neural morphology. Our data suggests 1H exposure does not impair hippocampal-dependent spatial or short-term memory in female mice.
2022-10-14 | PXD035933 | Pride
Project description:In vivo inhalation toxicity is typically tested in rodents by using either whole-body (WB) or nose-only (NO) exposure systems. To assess if cigarette smoke (CS)-induced disease endpoints would be similar after exposure in either system, we exposed apolipoprotein E-deficient mice to the same target total particulate matter concentration of mainstream smoke from 3R4F reference cigarettes in NO or WB exposure chambers (EC) for 2 months, and as controls to filtered air (Sham). While CS was reproducibly delivered to both exposure systems, we observed higher nicotine and formaldehyde concentrations being delivered to NOECs than to WBECs, but similar concentrations of carbon monoxide, acetaldehyde, and acrolein. CS exposure led to the adaptive changes expected in nasal epithelia, altered lung function, increased lung inflammation, and pronounced changes in the nasal epithelial transcriptome and lung proteome. Exposure in the NOEC caused generally more pronounced or severe respiratory effects and a higher stress response. Body weight, in particular, was much lower in mice exposed in the NOEC. Aortic arch imaging revealed greater plaque area in CS-exposed mice in the WBEC group than in the respective sham group. No difference was found in aortic plaque size between CS-exposed mice in the NOEC and sham groups. As CS is a chemically and temporarily dynamic aerosol, its composition in the breathing zone was not completely comparable between the two exposure systems; however, the main disease endpoints and exposure effects were largely induced in both systems. NO exposure appeared to be more stressful for the mice than WB exposure.
2021-03-16 | E-MTAB-9248 | biostudies-arrayexpress
Project description:Serum is an ideal source of biomarkers because of easy accessibility, noninvasiveness, and rapid response to disease. Given that the different clinical manifestation between early phase and late phase of sepsis, the change of serum proteins profile during different phase of sepsis can give insight into predictor for early diagnosis of sepsis. In this study, differential serum proteins were screened in mice treated with lipopolysaccharide (LPS) for 2 h, 24 h and controls using free-labeling coupled with two-dimensional liquid chromatography and tandem mass spectrometry (2D LC-MS/MS) technique.
2020-05-26 | PXD014259 | Pride
Project description:Interactions between stromal cell-derived factor-1M-NM-1 (SDF-1M-NM-1) and its cognate receptor CXCR4 are crucial for the recruitment of mesenchymal stem cells (MSCs) from bone marrow (BM) reservoirs to damaged tissues for repair during alarm situations. MicroRNAs are differentially expressed in stem cell niches, suggesting a specialized role in stem cell regulation. Here, we gain insight into the molecular mechanisms involved in regulating SDF-1M-NM-1. Individualized outcome prediction classifiers were successfully constructed through expression profiling of microRNAs (in all organisms as annotated in Sanger miRBase Release 11.0 (http://microrna.sanger.ac.uk))in one burned murine skin tissue compared to normal skin tissue,which had 57 upregulated microRNAs and 28 down-regulated microRNAs. In the study presented here, a consecutively operated, well-defined cohort of 2 cases, was used to acquire expression profiles of microRNAs (in all organisms as annotated in Sanger miRBase Release 11.0 (http://microrna.sanger.ac.uk)), leading to the successful construction of supervised. The most recent version of the array (v.11.0 - hsa, mmu & rno array) contains more than 1700 capture probes, covering all microRNAs annotated in miRBase 11.0, as well as all viral microRNAs, related to these species.
2013-05-02 | E-GEOD-46558 | biostudies-arrayexpress
Project description:Interactions between stromal cell-derived factor-1M-NM-1 (SDF-1M-NM-1) and its cognate receptor CXCR4 are crucial for the recruitment of mesenchymal stem cells (MSCs) from bone marrow (BM) reservoirs to damaged tissues for repair during alarm situations. MicroRNAs are differentially expressed in stem cell niches, suggesting a specialized role in stem cell regulation. Here, we gain insight into the molecular mechanisms involved in regulating SDF-1M-NM-1. Individualized outcome prediction classifiers were successfully constructed through expression profiling of microRNAs (in all organisms as annotated in Sanger miRBase Release 11.0 (http://microrna.sanger.ac.uk))in one burned murine skin tissue compared to normal skin tissue,which had 57 upregulated microRNAs and 28 down-regulated microRNAs In the study presented here, a consecutively operated, well-defined cohort of 2 cases, was used to acquire expression profiles of microRNAs(in all organisms as annotated in Sanger miRBase Release 11.0 (http://microrna.sanger.ac.uk)), leading to the successful construction of supervised .
2013-05-07 | E-GEOD-46660 | biostudies-arrayexpress
Project description:Chronic stress leads post-traumatic stress disorder (PTSD) and to metabolic complications, including fatty liver. It is feasible, that stress immediately initiates molecular mechanisms to alter energy metabolism and glucose homeostasis which interfere with hepatic lipid accumulation after stress recovery. We aim to elucidate these molecular mechanisms of long term stress effects on metabolism and focus on physiological adaptation and the role of FGF21, which is protective in hepatic lipid accumulation. Methods FGF21 knockout and control mice were exposed to chronic variable stress (Cvs) and recovered for 3 months to simulate PTSD. We determined in vivo and ex vivo energy metabolism, mitochondrial function by extracellular flux analysis, alterations in DNA modifying enzymes and gene regulation immediately after stress and after the recovery period to determine long term alterations. Results Chronic stress leads to reduced insulin sensitivity and hepatic lipid accumulation with increased fatty acid uptake (FAU), stress-induced lipolysis, and reduction in NAD+/NAD ratio and Sirt activity. Immediately after stress, PPARa and SREBP-1 target genes are differentially regulated and are involved in the development of stress-induced fatty liver. After recovery, insulin sensitivity increases but insulin-induced de novo lipogenesis (DNL) is reduced and FAU is increased. HDAC and MT activity are suppressed, whereas HAT activity increases, linking metabolic adjustments to transcriptional regulators. Thus, key metabolic genes are differentially regulated and secreted proteins indicate the activation of liver disease by Cvs only in FGF21WT. GR binding to the Cd36 promoter is altered. After stress recovery, serum FGF21 is increased and protects against lipid accumulation. FGF21 interacts by attenuating DNL, increasing FAU and HAT activity, and balancing mitochondrial activity. Higher long-term stress-induced activation and binding of GR to the FGF21 promoter may contribute to the prolonged FGF21 release. Conclusions We show that previous stress exposure determines predisposition to fatty liver disease is regulated by FGF21. Immediately after Cvs, altered gene regulation and activity of DNA-modifying enzymes determine the metabolic late effects seen in PTSD. FGF21 functions after chronic stress exposure i) to protect against hepatic lipid accumulation, ii) to maintain mitochondrial capacity, and iii) to mediate in the modulation of DNA-modifying enzymes. These findings highlight the protective role of FGF21 even in stress-induced hepatic lipid accumulation.
2022-03-10 | PXD025268 | Pride