Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA108277 | ENA |
REPOSITORIES: ENA
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Project description:Expression and function of the oncogenic transcription factor AP-1 (mainly composed of Jun and Fos proteins) is required for neoplastic transformation of mouse and human keratinocytes in vitro and tumor promotion as well as malignant progression in vivo. Here, we describe the identification of novel Fos target genes using global gene expression profiling with samples from a tumor model of mouse skin (K5-SOS-F). We could identify 366 differentially expressed genes comparing expression profiles from tumor samples of control animals with samples derived form mice with a specific deletion of fos in keratinocytes. Keywords: Fos-deletion, Fos-floxed, K5-SOS-F mouse tumor model, skin papilloma, global gene expression, microarray, Fos target in skin carcinogenesis
2008-09-01 | GSE10218 | GEO
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:Dowling-Meara type epidermolysis bullosa simplex (EBS-DM) is a severe blistering disease, caused by dominant mutations in either the keratin-5 (K5) or keratin-14 (K14) gene. K5 and K14 are the major components of the intermediate filament (IF) network in basal keratinocytes. Due to the dominant nature of EBS-DM, misfolded K5 or K14 proteins are incorporated into intermediate filaments, rendering them sensitive to mechanical stress. Upon trauma, these filaments disrupt and the keratinocytes lyse, leading to intra-epidermal blistering.The dominant nature of K5 and K14 mutations in EBS-DM represents a challenge to gene-therapeutic approaches. Therefore, we investigated the gene expression profile of a K14 mutant keratinocyte cell line (EBDM1) and compared it to the gene expression profile of a wild-type keratinocyte cell line (NEB1). The aim of this study was to identify differentially regulated genes as potential therapeutic targets for the development of new therapies.
2013-07-23 | E-MTAB-1641 | biostudies-arrayexpress
Project description:c-Fos, a member of the stress-activated Activator Protein 1 (AP-1) transcription factor family, is expressed in human hepatocellular cancer (HCC). Using genetically engineered mouse models (GEMMs) we show that hepatocyte-specific expression of c-Fos leads to a proliferative, de-differentiated phenotype, whereas hepatocyte-specific deletion of c-Fos protects against diethylnitrosamine (DEN)-induced liver cancer. Furthermore, c-Fos-expressing livers resemble human HCCs based on expression profiles. In the present RNA seq, we intend to analyze the transcriptomic profile of livers at 2 and 4 mo hepatocyte-specific c-Fos expression compared to the corresponding age-matched control mice. Moreover, we analyzed livers of mice with hepatocyte-specific deletion c-Fos at 48h after DEN treatment compared to identically treated control mice.
2017-03-23 | GSE81079 | GEO
Project description:Sos proteins are involved in the maintaining of skin homeostasis and participate in the initiation/progression of chemically-induced skin cancer. However, the precise role of these proteins in specific skin cellular compartments remains undetermined. Here, we examined the role of Sos1 and Sos2 in the overall transcriptional profile of mouse primary keratinocytes in order to unveil the specific functions of these Ras activators in keratinocyte population. We used microarrays to detail the impact of Sos1/2 depletion (individual or combined) in the transcriptional signature of mouse primary keratinocytes
2021-02-03 | GSE166020 | GEO
Project description:Dowling-Meara type epidermolysis bullosa simplex (EBS-DM) is a severe blistering disease, caused by dominant mutations in either the keratin-5 (K5) or keratin-14 (K14) gene. K5 and K14 are the major components of the intermediate filament (IF) network in basal keratinocytes. Due to the dominant nature of EBS-DM, misfolded K5 or K14 proteins are incorporated into intermediate filaments, rendering them sensitive to mechanical stress. Upon trauma, these filaments disrupt and the keratinocytes lyse, leading to intra-epidermal blistering. The dominant nature of K5 and K14 mutations in EBS-DM represents a challenge to gene therapeutic approaches. Therefore, we investigated the gene expression profile of a K14 mutant keratinocyte cell line (KEB7) and compared it to the gene expression profile of a wild-type keratinocyte cell line (NEB1). The aim of this study was to identify differentially regulated genes as potential therapeutic targets for the development of new therapies.
2013-07-23 | E-MTAB-1640 | biostudies-arrayexpress
Project description:Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. Global transcriptional profiling was utilized to evaluate the similarity between human psoriasis and the psoriasis-like phenotypes that develop in five mouse models (K5-Tie2, IMQ, K14-AREG, K5-Stat3C, K5-TGFbeta1)
2011-03-03 | GSE27628 | GEO
Project description:Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments. However, while many psoriasis mouse models have been proposed, no single model recapitulates all features of the human disease, and standardized validation criteria for psoriasis mouse models have not been widely applied. In this study, whole-genome transcriptional profiling is used to compare gene expression patterns manifested by human psoriatic skin lesions with those that occur in five psoriasis mouse models (K5-Tie2, imiquimod, K14-AREG, K5-Stat3C and K5-TGFbeta1). While the cutaneous gene expression profiles associated with each mouse phenotype exhibited statistically significant similarity to the expression profile of psoriasis in humans, each model displayed distinctive sets of similarities and differences in comparison to human psoriasis. For all five models, correspondence to the human disease was strong with respect to genes involved in epidermal development and keratinization. Immune and inflammation-associated gene expression, in contrast, was more variable between models as compared to the human disease. These findings support the value of all five models as research tools, each with identifiable areas of convergence to and divergence from the human disease. Additionally, the approach used in this paper provides an objective and quantitative method for evaluation of proposed mouse models of psoriasis, which can be strategically applied in future studies to score strengths of mouse phenotypes relative to specific aspects of human psoriasis. Global transcriptional profiling was utilized to evaluate the similarity between human psoriasis and the psoriasis-like phenotypes that develop in five mouse models (K5-Tie2, IMQ, K14-AREG, K5-Stat3C, K5-TGFbeta1) Expression patterns associated with mouse phenotypes were evaluated by comparing lesional skin from transgenic or IMQ-treated mice (n = 2-3) with normal skin obtained from control mice (n = 2-3).
2011-03-03 | E-GEOD-27628 | biostudies-arrayexpress
Project description:It is currently unclear whether tissue changes surrounding multifocal epithelial tumors are a cause or consequence of cancer. Here, we provide evidence that loss of mesenchymal Notch/CSL signaling causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumors. Mice carrying a mesenchymal-specific deletion of CSL/RBP-JK, a key Notch effector, exhibit spontaneous multifocal keratinocyte tumors that develop after dermal atrophy and inflammation. CSL-deficient dermal fibroblasts promote increased tumor cell proliferation through up-regulation of c-Jun and c-Fos expression and consequently higher levels of diffusible growth factors, inflammatory cytokines, and matrix remodeling enzymes. In human skin samples, stromal fields adjacent to cutaneous squamous cell carcinomas and multifocal premalignant actinic keratosis lesions exhibit decreased Notch/CSL signaling and associated molecular changes. Importantly, these changes in gene expression are also induced by UVA, a known environmental cause of cutaneous field cancerization and skin cancer. We used microarrays to detail the global changes in gene expression in dermal fibroblasts with in vivo and in vitro deletion of the RBP-Jk gene, compared to corresponding controls Global changes in gene expression in dermal fibroblasts with in vivo and in vitro deletion of the RBP-Jk gene were assessed, in parallel with the corresponding controls
2012-06-11 | E-GEOD-36359 | biostudies-arrayexpress
Project description:Expression data from keratinocyte-specific Zfp36-deficient mouse skin treated with imiquimod
| PRJNA354636 | ENA