Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-4066E-GEOD-4066
PROVIDER: PRJNA95191 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer.
2006-01-01 | S-EPMC1780187 | BioStudies
Project description:Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer. Keywords: time course, ultraviolet irradiation, UV, erbB2, mouse skin The dorsal skin of adult female CD-1 mice was clipped one day before treatment and shaved on the day of treatment. DMSO or 4 mg AG825 dissolved in DMSO was applied topically to the shaved back of the mice 2 h prior to exposure to 10 kJ/m^2 UV or sham irradiation. The UV dose was approximately 30% UVA, 70% UVB and <1% UVC, with a total output of 470 uW/cm^2. Flash frozen skin was removed and total RNA expracted with TRIzol reagent (Invitrogen) and further purified with an RNeasy kit (Qiagen). Amplification, reverse-transcription, biotinylation, and hybridization were all carried out under standard conditions and procedures recommended by the manufacturer.
2006-07-01 | E-GEOD-4066 | ArrayExpress
Project description:Exposure to ultraviolet (UV) irradiation is the major cause of nonmelanoma skin cancer, the most common form of cancer in the United States. UV irradiation has a variety of effects on the skin associated with carcinogenesis, including DNA damage and effects on signal transduction. The alterations in signaling caused by UV regulate inflammation, cell proliferation, and apoptosis. UV also activates the orphan receptor tyrosine kinase and proto-oncogene Erbb2 (HER2/neu). In this study, we demonstrate that the UV-induced activation of Erbb2 regulates the response of the skin to UV. Inhibition or knockdown of Erbb2 before UV irradiation suppressed cell proliferation, cell survival, and inflammation after UV. In addition, Erbb2 was necessary for the UV-induced expression of numerous proinflammatory genes that are regulated by the transcription factors nuclear factor-kappaB and Comp1, including interleukin-1beta, prostaglandin-endoperoxidase synthase 2 (Cyclooxygenase-2), and multiple chemokines. These results reveal the influence of Erbb2 on the UV response and suggest a role for Erbb2 in UV-induced pathologies such as skin cancer. Keywords: time course, ultraviolet irradiation, UV, erbB2, mouse skin Overall design: The dorsal skin of adult female CD-1 mice was clipped one day before treatment and shaved on the day of treatment. DMSO or 4 mg AG825 dissolved in DMSO was applied topically to the shaved back of the mice 2 h prior to exposure to 10 kJ/m^2 UV or sham irradiation. The UV dose was approximately 30% UVA, 70% UVB and <1% UVC, with a total output of 470 μW/cm^2. Flash frozen skin was removed and total RNA expracted with TRIzol reagent (Invitrogen) and further purified with an RNeasy kit (Qiagen). Amplification, reverse-transcription, biotinylation, and hybridization were all carried out under standard conditions and procedures recommended by the manufacturer.
2006-07-01 | GSE4066 | GEO
Project description:Epidemiological and experimental data implicate cutaneous human papillomavirus infection as co-factor in the development of cutaneous squamous cell carcinomas (cSCCs), particularly in immunocompromised organ transplant recipients (OTRs). Herein, we established and characterized a skin cancer model, in which Mus musculus papillomavirus 1 (MmuPV1) infection caused cSCCs in cyclosporine A (CsA)-treated mice, even in the absence of UV light. Development of cSCCs and their precursors were observed in 70% of MmuPV1-infected, CsA-treated mice on back as well as on tail skin. Immunosuppression by systemic CsA, but not UV-B irradiation, was a prerequisite, as immunocompetent or UV-B-irradiated mice did not develop skin malignancies after infection. In the virus-driven cSCCs the MmuPV1-E6/E7 oncogenes were abundantly expressed, and transcriptional activity and productive infection demonstrated. MmuPV1 infection induced the expression of phosphorylated H2AX, but not degradation of proapoptotic BAK in the cSCCs. Transfer of primary cells, established from a MmuPV1-induced cSCC from back skin, into athymic nude mice gave rise to secondary cSCCs, which lacked viral DNA, demonstrating that maintenance of the malignant phenotype was virus independent. This papillomavirus-induced skin cancer model opens future investigations into viral involvement, pathogenesis, and cancer surveillance, aiming at understanding and controlling the high incidence of skin cancer in OTRs.
2021-01-01 | S-EPMC7894140 | BioStudies
Project description:Ultraviolet B (UVB) exposure activates various inflammatory molecules of keratinocytes in the epidermis layer. Such UVB-mediated skin inflammation leaves post-inflammatory hyperpigmentation (PIH). Reports show a close relationship between PIH and high-mobility group box 1 (HMGB1) and its receptors. General clinical treatments of PIH, such as oral medication and laser treatment, have reported side effects. Recent studies reported the effects of radiofrequency (RF) irradiation on restoring dermal collagen, modulating the dermal vasculature, and thickening the basement membrane. To validate how RF regulates the inflammatory molecules from UVB-irradiated keratinocytes, we used UVB-radiated keratinocytes and macrophages, as well as animal skin. In addition, we examined two cases of RF-irradiated skin inflammatory diseases. We validated the effects of RF irradiation on keratinocytes by measuring expression levels of HMGB1, Toll-like receptors (TLRs), and other inflammatory factors. The results show that the RF modulates UVB-radiated keratinocytes to secrete fewer inflammatory factors and also modulates the expression of macrophages from HMGB1, TLRs, and inflammatory factors. RF irradiation could alleviate inflammatory skin diseases in patients. RF irradiation can regulate the macrophage indirectly through modulating the keratinocyte and inflammatory molecules of macrophages reduced in vitro and in vivo. Although the study is limited by the low number of cases, it demonstrates that RF irradiation can regulate skin inflammation in patients.
2021-01-01 | S-EPMC7957621 | BioStudies
Project description:Recent studies show that IL-22, a cytokine produced by activated CD4+ T cells and NK cells, plays a pathogenic role in acute and chronic skin diseases. While IL-22 is produced by immune cells, the expression of IL-22R?, the functional subunit of IL-22R, is mostly restricted to non-hematopoietic cells in organs such as the skin and pancreas. Although it is well known that ultraviolet B (UVB) radiation induces skin inflammation, there have been no reports regarding the effect of UVB on the expression of IL-22R?. This study investigated IL-22R? expression and IL-22-mediated proliferation and pro-inflammatory cytokine production by UVB-irradiated keratinocytes. IL-22R? was increased in HaCaT and primary human keratinocytes after UVB irradiation through the translocation of IL-22R? from the cytosol to the membrane. This increase in the expression of IL-22R? was mediated by the PI3K/Akt pathway. Moreover, the suppression of keratinocyte proliferation by UVB irradiation was inhibited by treatment with IL-22. At the same time, IL-22 increased the production of IL-1?, IL-6, and IL-18 in UVB-irradiated HaCaT cells and primary human keratinocytes. Finally, IL-22R? expression was increased in UVB-irradiated human and mouse skin by immunohistochemistry. The increased expression of IL-22R? therefore promotes keratinocyte proliferation and pro-inflammatory cytokine production during UVB-induced skin inflammation, suggesting that UVB facilitates skin inflammation by increasing the responsiveness of keratinocytes to IL-22. This study provides a new insight into UVB-induced skin inflammation and the regulation of related inflammatory skin diseases.
2017-01-01 | S-EPMC5448782 | BioStudies
Project description:The skin provides protection against external stimuli; however, solar radiation, including ultraviolet A (UVA) and ultraviolet B (UVB), can result in profound influences on skin structure and function, which eventually impairs its molecular characteristics and normal physiology. In the current study, we performed proteome tools combined with an immunohistological approach on nude mouse skin to evaluate the adverse responses elicited by UVA and UVB irradiation, respectively. Our findings indicated that UVA significantly promotes oxidative damage in DNA, the breakdown of collagen fiber in the dermis, and the apoptosis of fibroblasts, which leads to inflammation. Meanwhile, UVB administration was found to enhance the carbonylation of various proteins and the proliferation of keratinocyte. Particularly, raspberry extract, which has been confirmed to have antioxidative efficacy, could effectively attenuate ultraviolet (UV) radiation-caused cell death. Network analysis also implied that UVA and UVB induce quite different responses, and that UVA results in cell death as well as inflammation mediated by caspase-3 and activator protein 1/nuclear factor kappa-light-chain-enhancer of activated B cells (AP-1/NF-?B), while UVB predominantly increases the risk of skin carcinogenesis involved with oncogenes such as p53 and c-Myc. Taken together, functional proteomics coordinated with histological experiments could allow for a high-throughput study to explore the alterations of crucial proteins and molecules linked to skin impacts subjected to UVA and UVB exposure.
2019-01-01 | S-EPMC6943602 | BioStudies
Project description:Solar ultraviolet (sUV) irradiation is a major environmental carcinogen that can cause inflammation and skin cancer. The costs and morbidity associated with skin cancer are increasing, and therefore identifying molecules that can help prevent skin carcinogenesis is important. In this study, we identified the p53-related protein kinase (PRPK) as a novel oncogenic protein that is phosphorylated by the T-LAK cell-originated protein kinase (TOPK). Knockdown of TOPK inhibited PRPK phosphorylation and conferred resistance to solar-simulated light (SSL)-induced skin carcinogenesis in mouse models. In the clinic, acute SSL irradiation significantly increased epidermal thickness as well as total protein and phosphorylation levels of TOPK and PRPK in human skin tissues. We identified two PRPK inhibitors, FDA-approved rocuronium bromide (Zemuron®) or betamethasone 17-valerate (Betaderm®) that could attenuate TOPK-dependent PRPK signaling. Importantly, topical application of either rocuronium bromide or betamethasone decreased SSL-induced epidermal hyperplasia, neovascularization, and cutaneous squamous cell carcinoma (cSCC) development in SKH1 (Crl: SKH1-Hrhr) hairless mice by inhibiting PRPK activation, and also reduced expression of the proliferation and oncogenesis markers, COX-2, cyclin D1, and MMP-9. This study is the first to demonstrate that targeting PRPK could be useful against sUV-induced cSCC development.
2018-01-01 | S-EPMC6195829 | BioStudies
Project description:Transforming growth factor beta 1 (TGF?1) is a pleiotropic cytokine in the skin that can function both as a tumor promoter and suppressor in chemically induced skin carcinogenesis, but the function in ultraviolet B (UVB) carcinogenesis is not well understood. Treatment of SKH1 hairless mice with the activin-like kinase 5 (ALK5) inhibitor SB431542 to block UVB-induced activation of cutaneous TGF?1 signaling suppressed skin tumor formation but did not alter tumor size or tumor cell proliferation. Tumors that arose in SB-treated mice after 30 weeks had significantly reduced percentage of IFN?(+) tumor-infiltrating lymphocytes compared with control mice. SB431542 blocked acute and chronic UVB-induced skin inflammation and T-cell activation in the skin-draining lymph node (SDLN) and skin but did not alter UVB-induced epidermal proliferation. We tested the effect of SB431542 on migration of skin dendritic cell (DC) populations because DCs are critical mediators of T-cell activation and cutaneous inflammation. SB431542 blocked (i) UVB-induced Smad2 phosphorylation in dermal DC (dDC) and (ii) SDLN and ear explant migration of CD103(+) CD207(+) and CD207(-) skin DC subsets but did not affect basal or UV-induced migration of Langerhans cells. Mice expressing a dominant-negative TGF? type II receptor in CD11c(+) cells had reduced basal and UVB-induced SDLN migration of CD103(+) CD207(+) and CD207(-) DC subsets and a reduced percentage of CD86(high) dDC following UVB irradiation. Together, these suggest that TGF?1 signaling has a tumor-promoting role in UVB-induced skin carcinogenesis and this is mediated in part through its role in UVB-induced migration of dDC and cutaneous inflammation.
2014-01-01 | S-EPMC3977148 | BioStudies
Project description:BACKGROUND: Mus spretus diverged from Mus musculus over one million years ago. These mice are genetically and phenotypically divergent. Despite the value of utilizing M. musculus and M. spretus for quantitative trait locus (QTL) mapping, relatively little genomic information on M. spretus exists, and most of the available sequence and polymorphic data is for one strain of M. spretus, Spret/Ei. In previous work, we mapped fifteen loci for skin cancer susceptibility using four different M. spretus by M. musculus F1 backcrosses. One locus, skin tumor susceptibility 5 (Skts5) on chromosome 12, shows strong linkage in one cross. RESULTS: To identify potential candidate genes for Skts5, we sequenced 65 named and unnamed genes and coding elements mapping to the peak linkage area in outbred spretus, Spret/EiJ, FVB/NJ, and NIH/Ola. We identified polymorphisms in 62 of 65 genes including 122 amino acid substitutions. To look for polymorphisms consistent with the linkage data, we sequenced exons with amino acid polymorphisms in two additional M. spretus strains and one additional M. musculus strain generating 40.1 kb of sequence data. Eight candidate variants were identified that fit with the linkage data. To determine the degree of variation across M. spretus, we conducted phylogenetic analyses. The relatedness of the M. spretus strains at this locus is consistent with the proximity of region of ascertainment of the ancestral mice. CONCLUSION: Our analyses suggest that, if Skts5 on chromosome 12 is representative of other regions in the genome, then published genomic data for Spret/EiJ are likely to be of high utility for genomic studies in other M. spretus strains.
2008-01-01 | S-EPMC2628916 | BioStudies