Development of gene expression signatures for barrier recovery phase in epidermis from acute barrier disruption
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PROVIDER: PRJNA612526 | ENA |
REPOSITORIES: ENA
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Project description:The skin barrier consists of multiple lipid-enriched layers. Sodium lauryl sulfate is a well-known substance that can disrupt the skin barrier. The mechanisms underlying the barrier repair process, especially the influence of topical sodium lauryl sulfate treatment in the barrier recovery phase remain unresolved. To understand the process of reconstruction of the intercellular lipid layer of the skin after acute barrier disruption by sodium lauryl sulfate treatment in vivo.
2023-01-01 | GSE146969 | GEO
Project description:Keratinocytes respond to environmental signals by eliciting induction of genes that preserve skin’s integrity. Here we show that the transcriptional response to stress signaling is supported by short-lived epigenetic changes. Comparison of chromatin accessibility and transcriptional changes induced by barrier disruption or by loss of the nucleosome remodeler Mi-2β identified their striking convergence in mouse and human keratinocytes. Mi-2β directly repressed genes induced by barrier disruption by restricting AP1-enriched promoter-distal sites, occupied by Mi-2β and JUNB at steady state and by c-JUN after Mi-2β depletion or stress signaling. Barrier disruption led to a modest reduction in Mi-2β expression and a further selective reduction of Mi-2β localization at stress response genes possibly through competition with activated c-JUN. Consistent with a repressive role at stress response genes, genetic ablation of Mi-2β did not prevent re-establishment of barrier integrity but was required for return to homeostasis. Thus a competition between Mi-2β repressive and activating AP1 complexes may permit rapid transcriptional response to and resolution from stress signaling.
2019-12-03 | GSE139685 | GEO
Project description:Functional interactions between Mi-2β and AP1 complexes control response and recovery from barrier disruption
| PRJNA586885 | ENA
Project description:To identify putative gene regulatory regions that respond to epidermal injury, we mapped chromatin dynamics in a stratified human epidermis during barrier maturation and disruption. Engineered skin substitutes (ESS) cultured at the air-liquid interface were used as a model of developing human epidermis with incomplete barrier formation. The epidermal barrier stabilized following engraftment onto immunocompromised mice, and was compromised again upon injury. Modified formaldehyde-assisted isolation of regulatory elements (FAIRE) was used to identify accessible genomic regions characteristic of monolayer keratinocytes, ESS in vitro, grafted ESS, and tape-stripped ESS graft. We mapped differentiation- and maturation-associated changes in transcription factor binding sites enriched at each stage and observed overrepresentation of AP-1 gene family motifs in barrier- deficient samples. Transcription of TSLP, an important effector of immunological memory in response to allergen exposure, was dramatically elevated in our barrier-deficient samples. We identified dynamic DNA elements that correlated with TSLP induction and may contain enhancers that regulate TSLP. Two dynamic regions were located near the TSLP promoter and overlapped with allergy-associated SNPs rs17551370 and rs2289877, strongly implicating these loci in the regulation of TSLP expression in allergic disease. Additional dynamic chromatin regions ~250kb upstream of the TSLP promoter were found to be in high linkage disequilibrium with allergic disease SNPs. Taken together, these results define dynamic chromatin accessibility changes during epidermal development and dysfunction.
2017-08-28 | GSE101835 | GEO
Project description:We generated KA mutant mice (Krt14-CreERT + ABCA12-flox/flox) and controls (ABCA12-flox/flox) that enabled us to assess the effects of deleting a critical barrier gene, ABCA12, in the skin epidermis following tamoxifen treatment. These studies identified numerous differentially expressed genes (DEGs) upon barrier disruption/ABCA12 deletion, including compensatory upregulation of genes involved with epidermal differentiation and barrier function. Overall, this data-set provides a global view of molecular changes that occur in adult mouse skin following barrier perturbation.
2024-05-20 | GSE254889 | GEO
Project description:Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to play a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of the gram-positive pathogenic and reduction of bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management. In this study, we establish a link between the two phenomena, namely gut barrier compromise and dysregulated bile acid metabolism. We show for the first time that morphine fosters significant gut microbial dysbiosis and disrupts cholesterol/bile acid metabolism. Changes in the gut microbial composition is strongly correlated to disruption in host inflammatory homeostasis13,14 and in many diseases (e.g. cancer/HIV infection), persistent inflammation is known to aid and promote the progression of the primary morbidity. We show here that chronic morphine, gut microbial dysbiosis, disruption of cholesterol/bile acid metabolism and gut inflammation; have a linear correlation. This opens up the prospect of devising minimally invasive adjunct treatment strategies involving microbiome and bile acid modulation and thus bringing down morphine-mediated inflammation in the host.
2016-06-01 | E-MTAB-3722 | biostudies-arrayexpress
Project description:Investigation of molecular mechanisms of impaired skin barrier by ATRA in mouse epidermis
2018-12-21 | GSE124181 | GEO
Project description:Epidermal barrier repair mechanisms activated in psoriasis lesions are likely involved in limiting the severity of this disease. We show that loss of grainyhead-like 3 (Grhl3), a pro-terminal differentiation factor in the epidermis, is sufficient to trigger greater sensitivity to and delayed resolution of epidermal lesions resulting from either physical or immune mediated barrier injury. After stimulation of Toll like receptors, the loss of Grhl3 resulted in increased epidermal damage with a striking increase in basal cell proliferation, hyperplasia of partially differentiated suprabasal layers, and a transcriptional profile highlighted by the overexpression of epidermal wound response and alarmin genes. This study reveals an important role for the epidermis in the initiation and recovery from immune-mediated lesions, and indicated that the epidermal regulator Grhl3 acts to both suppress disease initiation and resolve existing lesions. This work suggests that treatments focused on improving barrier function could be used preventatively and therapeutically in psoriasis. Whole skin was collected from E16.5 mouse backskins for Grhl3 ChIP. Adult epidermis for depilation and imiquimod experiments was seperated from dermis using dispase prior to Grhl3 ChIP.
2014-09-01 | E-GEOD-52648 | biostudies-arrayexpress
Project description:Epidermis Kif3a knockout transcriptome reveals genes involved in skin barrier homeostasis
| PRJNA637026 | ENA
Project description:BackgroundRecent advances in sequencing technologies have enabled metagenomic analyses of many human body sites. Several studies have catalogued the composition of bacterial communities of the surface of human skin, mostly under static conditions in healthy volunteers. Skin injury will disturb the cutaneous homeostasis of the host tissue and its commensal microbiota, but the dynamics of this process have not been studied before. Here we analyzed the microbiota of the surface layer and the deeper layers of the stratum corneum of normal skin, and we investigated the dynamics of recolonization of skin microbiota following skin barrier disruption by tape stripping as a model of superficial injury.ResultsWe observed gender differences in microbiota composition and showed that bacteria are not uniformly distributed in the stratum corneum. Phylogenetic distance analysis was employed to follow microbiota development during recolonization of injured skin. Surprisingly, the developing neo-microbiome at day 14 was more similar to that of the deeper stratum corneum layers than to the initial surface microbiome. In addition, we also observed variation in the host response towards superficial injury as assessed by the induction of antimicrobial protein expression in epidermal keratinocytes.ConclusionsWe suggest that the microbiome of the deeper layers, rather than that of the superficial skin layer, may be regarded as the host indigenous microbiome. Characterization of the skin microbiome under dynamic conditions, and the ensuing response of the microbial community and host tissue, will shed further light on the complex interaction between resident bacteria and epidermis.
| S-EPMC3580493 | biostudies-literature