Project description:Psoriasis is a common inflammatory skin disease characterized by aberrant inflammation and epidermal hyperplasia. Molecular mechanisms that regulate psoriasis-like skin inflammation remain to be fully understood. Here we show that the expression of Ovol1 transcription factor is upregulated in psoriatic skin, and its deletion results in aggravated psoriasis-like skin symptoms following stimulation with imiquimod (IMQ). Using bulk and single-cell RNA-sequencing, we identify molecular changes in the epidermal, fibroblast and immune cells of Ovol1-deficient skin that reflect altered course of epidermal differentiation and enhanced inflammatory responses. Furthermore, we provide evidence for excessive full-length IL-1 signaling in the microenvironment of IMQ-treated Ovol1-deficient skin that functionally contributes to immune cell infiltration and epidermal hyperplasia. Collectively, our study uncovers a protective role for Ovol1 in curtailing psoriasis-like inflammation and the associated skin pathology

2021-12-01 | GSE159704 | GEO

Transgenic overexpression of Pla2g2f at a level relevant to skin pathology display alopecia and psoriasis-like epidermal hyperplasia

Project description:Pla2g2f is dominantly expressed in the suprabasal layer of mouse epidermis. Microarray gene profiling supported the overall tendency of epidermal and sebaceous gland hyperplasia as well as alopecia in Pla2g2f-transgenic skin. Pla2g2f-Tg/+ mice and littermate controls (C57BL/6 background); 25-day old; skin; pooled from 4 mice for each genotype.

2015-08-08 | E-GEOD-71829 | biostudies-arrayexpress

Broad defects in epidermal cornification in atopic dermatitis (AD) identified through genomic analysis

Project description:In this study we used genomic profiling to characterize differences in expression of genes related to epidermal growth/differentiation and inflammatory circuits in skin lesions of psoriasis and atopic dermatitis (AD), comparing expression values to normal skin. Skin biopsies were collected from 9 patients with chronic atopic dermatitis, 15 psoriasis patients, and 9 healthy volunteers. Keywords: Genetic-pathology Psoriasis and AD are common inflammatory skin diseases which share important features, including: 1) large infiltrates of T-cells and inflammatory dendritic cells in skin lesions, 2) immune activation with up-regulated expression of many cytokines, chemokines, and inflammatory molecules 3) marked epidermal hyperplasia in chronic diseased skin and 4) defective barrier function with increased transepidermal water loss (TEWL), which reflects underlying alterations in keratinocyte differentiation. Using genomic profiling we provide a comprehensive comparison of chronic psoriasis and AD skin lesions as compared with normal skin.

2009-10-31 | E-GEOD-16161 | biostudies-arrayexpress

Grhl3 is essential for epidermal barrier repair from both physical and immune injury, relevance to lesional skin disease

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

Expression data from mouse adult epidermis in response to physical or immune mediated damage

Project description:Whether epidermal factors play a primary role in immune-mediated skin diseases such as psoriasis is unknown. We now show that the pro-differentiation transcription factor Grainyhead-like 3 (GRHL3), essential during epidermal development but dispensable in adult skin homeostasis, is required for barrier repair after adult epidermal injury. Consistent with activation of a GRHL3-regulated repair pathway in psoriasis, we find GRHL3 up-regulation in lesional skin where GRHL3 binds known epidermal differentiation gene targets. Furthermore, we show the functionality of this pathway in the Imiquimod mouse model of immune-mediated epidermal hyperplasia where loss of Grhl3 exacerbates the epidermal damage response, conferring greater sensitivity to disease induction, delayed resolution of epidermal lesions, and resistance to anti-IL-22 therapy. ChIP-seq and gene expression profiling studies show that while GRHL3 regulates differentiation genes both in development and during repair from immune-mediated damage, it targets distinct sets of genes in the two processes. In particular, GRHL3 suppresses a number of alarmin and other pro-inflammatory genes after immune injury. This study identifies a GRHL3-regulated epidermal barrier repair pathway that suppresses disease initiation and helps resolve existing lesions in immune-mediated epidermal hyperplasia. A single timepoint was assessed after physical injury of the epidermal barrier and two timepoints were assessed after immune mediated injury of the epidermis following Imiquimod treatment (psoriasis mouse model)

2014-10-01 | E-GEOD-59384 | biostudies-arrayexpress

Gene expression in psoriasis lesions and uninvolved skin

Project description:Psoriasis is a chronic inflammatory skin disease characterized by marked proliferation of keratinocytes leading to pronounced epidermal hyperplasia, elongation of rete ridges and hyperkeratosis. The most common form of psoriasis, chronic plaque psoriasis (Psoriasis vulgaris), involves relatively stable occurrence and progression of sharply demarcated lesions, usually on the trunk and extremities, which share a combination of trademark histological features, including tortuous and dilated dermal capillaries, loss of the epidermal granular layer, and accumulation of neutrophils beneath parakeratotic scale. In this study, whole-genome transcriptional profiling was used to characterize gene expression in 4 lesional and uninvolved skin samples obtained from patients with stable chronic plaque psoriasis. Skin mRNA expression was analysed by microarray. Four individuals with chronic plaque psoriasis were enrolled. 6 mm punch biopsies were obtained under local anaesthesia (lidocaine) from uninvolved skin and a target plaque.

2013-12-10 | E-GEOD-50790 | biostudies-arrayexpress

Hair follicle stem cells (HF-SCs) can initiate psoriasis-like disease in mice

Project description:Using lineage-tracing in a well-established psoriasis-like mouse model with inducible epidermal deletion of c-Jun and JunB, we found that mutant HF-SCs survive and express a broad group of pro-inflammatory cytokines, whereas mutant inter-follicular epidermal cells (IFE) disappear over time. Mutant HF-SCs initiate epidermal hyperplasia and skin inflammation by priming neighboring non-mutant epidermal cells to acquire a psoriasis-like phenotype. To explore the molecular mechanisms that govern the behavior of these distinct mutant and non-mutant HF-SCs and IFE cell populations during psoriasis-like disease, RNA sequencing analyses of sorted GFP+, Tomato+ HF-SCs and b-KCs from DKO*-mT/mG mice.

2019-08-23 | GSE119762 | GEO

Grhl3 is essential for epidermal barrier repair from both physical and immune injury, relevance to lesional skin disease

2014-09-01 | GSE52648 | GEO