UBE2N function in skin homeostasis and immunity
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE249200 | GEO | 2024/04/03
REPOSITORIES: GEO
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Project description:UBE2N function in skin homeostasis and immunity
| PRJNA1047658 | ENA
Project description:This study investigates the role of ADAM17 (a disintegrin and metalloproteinase 17) in skin homeostasis. Here, we show that mice lacking ADAM17 in keratinocytes have a normal epidermal barrier and skin architecture at birth, but develop pronounced defects in epidermal barrier integrity soon after birth and chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 days after birth, followed by transepidermal water loss and inflammatory immune cell infiltration. Our results identify a previously unappreciated critical role of the ADAM17/EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier. The genome-wide effects of ADAM17 deficiency were analyzed using Agilent Whole Mouse Genome microarrays. Conditional keratinocyte-specific ADAM17 knockout mice were generated by crossing Adam17flox/flox mice with keratin-14-Cre (Krt14-Cre) transgenic mice. Adam17flox/+Krt14-Cre mice were mated with Adam17flox/flox mice to generate pups of Adam17flox/flox Krt14-Cre positive (cKO) and Krt14-Cre negative (wild-type) control littermates. The genetic background was a mix of 129Sv and C57BL/6. As material, back skin tissue biopsies (postnatal day 10) from n = 2 wild-type skin and n = 2 ADAM17 epidermal KO skin (matched WT-cKO pairs from two different litters) were used in this study.
2012-06-20 | E-GEOD-38830 | biostudies-arrayexpress
Project description:Essential to terrestrial life is the formation of a competent skin barrier that prevents desiccation and entry by harmful substances. A tightly orchestrated series of cellular changes is required for the proper formation of the epidermal permeability barrier. These changes occur in the context of the commensal skin microbiota. Using germ free mice and antibiotic depletion models, we demonstrate the microbiota is necessary for proper differentiation and repair of the barrier. These effects were mediated by keratinocyte signaling through the aryl hydrocarbon receptor (AHR), a xenobiotic receptor that also regulates epidermal differentiation. Murine skin lacking keratinocyte AHR was more susceptible to infection by S. aureus and increased pathology in a model of atopic dermatitis. Topical colonization with a defined consortium of human skin commensals restored barrier competence in germ free skin and during epicutaneous sensitization; these effects were dependent on keratinocyte AHR. We reveal a fundamental role for the commensal skin microbiota in directing skin barrier formation and repair through the AHR, with far-reaching implications for the numerous skin disorders characterized by disrupted epidermal differentiation and/or barrier competence.
2021-03-31 | GSE162925 | GEO
Project description:Atopic dermatitis (AD) is a common chronic inflammatory skin disorder characterized by disrupted epidermal barrier function and aberrant immune responses. Despite recent developments in new treatments for AD, there are still unmet needs for the disease management due to its complex and multifactorial nature. Recent genome-wide association studies (GWAS) have identified NLRP10 as an AD susceptible gene. However, the physiological role of NLRP10 in skin homeostasis and its relevance to AD are unknown. Here we show that NLRP10 promotes keratinocyte survival and facilitates epidermal differentiation and barrier function. Mechanistically, NLRP10 limits cell death by preventing the recruitment of caspase-8 onto the death inducing signaling complex and inhibiting its subsequent activation. NLRP10 also stabilizes p63, the master regulator of keratinocyte differentiation, to drive proper keratinocyte differentiation and to reinforce the barrier function. Importantly, NLRP10 is downregulated in AD skin samples. Our findings underscore NLRP10 as a key player in atopic dermatitis pathogenesis, highlighting NLRP10 as a potential target for therapeutic intervention to restore skin barrier function and homeostasis in AD.
2024-10-17 | GSE264616 | GEO
Project description:The morphology of the skin changes upon depletion of MCPIP1 in cells of myeloid origin as well as in keratinocytes. The thicknesses of epidermal and hypodermal layers are significantly increased in mice with loss of epidermal MCPIP1, whereas loss of myeloid MCPIP1 exerts completely opposite effect. Both types of mice show contrary response to the stimulation with 12-O-tetradecanoylphorbol-13-acetate. Skin morphology and inflammatory phenotype of keratinocyte- and myeloid- double MCPIP1 knockout mice is similar to that of the single keratinocyte knockout of MCPIP1. In all, myeloid and epidermal MCPIP1 play significant but distinct roles in the modulation of skin-related processes.
2024-07-09 | GSE253656 | GEO
Project description:Skin homeostasis is guided by spatiotemporal regulation of gene expression, establishing each stage of keratinocyte differentiation. The current study presents transcriptomic and chromatin profiling for the proliferating (basal) and differentiated (suprabasal) cell populations derived from neonate mice (p0-p2) skin epidermis. This multi-omic approach will enable idenitification of cell specific epidermal cross-talk central to the equlibirum.
2023-01-13 | GSE197018 | GEO
Project description:This study investigates the role of ADAM17 (a disintegrin and metalloproteinase 17) in skin homeostasis. Here, we show that mice lacking ADAM17 in keratinocytes have a normal epidermal barrier and skin architecture at birth, but develop pronounced defects in epidermal barrier integrity soon after birth and chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 days after birth, followed by transepidermal water loss and inflammatory immune cell infiltration. Our results identify a previously unappreciated critical role of the ADAM17/EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier.
2012-06-21 | GSE38830 | GEO
Project description:Skin homeostasis is guided by spatiotemporal regulation of gene expression, establishing each stage of keratinocyte differentiation. The current study presents transcriptomic and chromatin profiling for the proliferating (basal) and differentiated (suprabasal) cell populations derived from neonate mice (p0-p2) skin epidermis. This multi-omic approach will enable idenitification of cell specific epidermal cross-talk central to the equlibirum.
2023-01-12 | GSE206556 | GEO
Project description:The skin epidermis is a constantly renewing stratified epithelial tissue that provides essential protective barrier functions. The major barrier is at the outermost layers of the epidermis, formed by terminally differentiated keratinocytes reinforced by proteins and lipids of their cornified envelope (CE), and disruptions to this process characterizes common skin disorders. ZNF750 is an epithelial transcription factor essential for in vitro keratinocyte differentiation, whose autosomal dominant mutation in humans causes psoriasis-like skin disease. Here, we report epidermal-specific Znf750 conditional knockout mouse model utilized to uncover the role of Znf750 in epidermal development. We show that deletion of Znf750 in the developing skin does not block epidermal differentiation, suggesting in vivo compensatory feedback mechanisms, yet results in impaired barrier function and perinatal lethality. Molecular dissection uncovered ultrastructural defects in the differentiated layers of the epidermis, accompanied by alterations in the expression of ZNF750-dependent genes encoding for key proteins and lipids involved in CE formation, including gene subsets known to be mutated in skin disease with impaired barrier function.
2023-08-01 | GSE235032 | GEO
Project description:It has long been known that excessive mitotic activity due to H-Ras can block keratinocyte differentiation and cause skin cancer. It is not clear, however, whether there are any innate surveillants that ensure keratinocytes undergoing terminal differentiation, preventing the disease. IKKα induces keratinocyte terminal differentiation and its reduction promotes skin tumor development. However, its nature function in skin cancer is unknown. Here we found that mice with IKKα deletion in keratinocytes or in hair follicle keratinocytes developed a thickened epidermis and spontaneous squamous cell-like carcinomas. Inactivation of epidermal growth factor receptor (EGFR) or reintroduction of IKKα inhibited excessive mitosis, induced terminal differentiation, and prevented skin cancer through an EGFR-driven autocrine loop in mice. Thus, IKKα serves as an innate surveillant.
2009-07-14 | GSE12111 | GEO