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.
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
Project description:Canine atopic dermatitis (AD) is clinically similar to human AD, implicating it as a useful model of human eosinophilic allergic disease. To identify cutaneous gene transcription changes in relatively early inflammation of canine AD, microarrays were used to monitor transcription in normal skin (n=13) and in acute lesional AD (ALAD) and nearby visibly nonlesional AD (NLAD) skin (n=13) from dogs. Scanning the putative abnormally-transcribed genes, several potentially relevant genes, some abnormally transcribed in both NLAD and ALAD (e.g. IL6, NFAM1, MSRA, and SYK), were observed. Comparison for abnormally-transcribed genes common to two related human diseases, human AD and asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP), further identified genes or gene sets likely relevant to eosinophilic allergic inflammation. These included 1) genes associated with alternatively-activated monocyte-derived cells, including members of the monocyte chemotactic protein (MCP) gene cluster, 2) members of the IL1 family gene cluster, 3) eosinophil-associated seven transmembrane receptor EMR1 and EMR3 genes, 4) interferon-inducible genes, and 5) keratin genes associated with hair and nail formation. Overall, numerous abnormally-transcribed genes were observed only in canine AD; however, many others are common to related human eosinophilic allergic diseases and represent therapeutic targets testable in dogs with AD. Total RNA from skin biopsy specimens from 13 Healthy (i.e. Normal) dogs were compared to total RNA from acute lesional skin biopsy specimens (i.e. ALAD) and nearby visibly nonlesional skin biopsy specimens (i.e. NLAD) from 13 dogs with atopic dermatitis.
Project description:Hedgehog (Hh) proteins are morphogens which regulate embryonic development and adult tissue homeostasis, with distinct outcomes dependent on the strength and duration of their signals. We show that the Hh signalling pathway modulates the induction and pathology of mouse atopic dermatitis. Sonic hedgehog (Shh) and Hh pathway target genes were upregulated on induction of atopic dermatitis, and the Hh pathway was activated in skin T cells, showing that they respond in vivo to Hh signals secreted from the skin. Shh upregulation reduced skin inflammation in mice, whereas pharmacological Smoothened-inhibition reduced Shh upregulation and exacerbated skin pathology. Hh-signalling to T cells prevented skin inflammation on induction of dermatitis, while inhibition of Hh-mediated transcription in T cells substantially exacerbated the disease. RNA-sequencing analysis of skin CD4+ T cells from mice with chronic atopic dermatitis revealed decreased expression of immune regulatory genes in mice with conditional inhibition of Hh-mediated transcription in T cells, and increased expression of inflammatory and chemokine genes. In contrast, constitutive Hh mediated transcription in T cells led to increased expression of immune regulatory genes in skin CD4+ T cells from mice with chronic atopic dermatitis and protected against inflammation. Hh-mediated transcription in T cells resulted in increased regulatory T (Treg) cells in the periphery and skin of dermatitis-induced mice, and increased TGF-β expression, supporting their immunoregulatory phenotype, whereas, inhibition of T cell specific Hh-mediated transcription, resulted in impaired Treg function, which permitted progression of skin inflammation.
Project description:Recently, it was shown that lesional skin of atopic dermatitis patients expresses low levels of some antimicrobial peptides, compared with psoriasis patients. Here we performed microarray analysis on mRNA from purified lesional epidermal cells of patients with chronic plaque psoriasis and chronic atopic dermatitis, to investigate whether this is a general phenomenon for host defense proteins, and how specific it is for this class of molecules. We found overexpression of many antimicrobial genes in keratinocytes from psoriatic skin compared with atopic dermatitis skin. Interestingly, we observed that markers of normal differentiation and the activated/hyperproliferative epidermal phenotype were expressed at equal levels. Chronic lesions of psoriasis and atopic dermatitis patients are remarkably similar with respect to cellular proliferation. We conclude that psoriatic epidermis expresses high levels of host defense proteins compared with atopic dermatitis epidermis, and this phenomenon appears to be specific for these proteins. It remains to be investigated whether this is caused by genetic polymorphisms in pathways leading to an epidermal antimicrobial response, or by differences in the cellular infiltrate in psoriasis compared with atopic dermatitis. In general the microarray technique is used to probe a (very large) number of genes for say the deseased and the healthy state.Then gene ontology is used to detect the involved pathways.We did not set out to find a comprehensive list of genes involved in these skin deseases.We do suspect that the "path way" approach might be a bit anthropomorphic.Here we offered a different approach.We set out to investigate the evolutionary fitness changes from one local maximum , Psoriasis , to another , Atopie. Our hypothesis is that Psoriasis is at one extreme in the reaction of the evolution to invading micro organisms and Atopie at an other.So the vast chemical web called human being with numorous feedback and feed forward signals would then be tilted a bit in multidimensional Gene Space and the microarray technique would show us a glimpse of the involved genes. Keywords: Disease state analysis
Project description:Atopic dermatitis (AD) is the chronic inflammatory skin disease accompanied with severe pruritus. To explore the roles of EGR1 in atopic dermatitis and the relationship between EGR1 and pruritus-scratching behavior, we used a atopic dermatitis-like mouse model driven by house dust mite (HDM) treatment in wild type and EGR1 KO mice, followed with RNA-sequencing analysis.
Project description:Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in children characterized by dermatitis and pruritus. MicroRNAs (miRNAs) have been shown as great potential biomarkers for disease fingerprints to predict prognostics. We aimed to identify miRNA signature from serum and urine for the prognosis of AD patient by genome-wide miRNA profiling analysis. Serum from 8 children with AD and 8 healthy children were collected
Project description:Atopic dermatitis (AD) is the most prevalent chronic inflammatory skin disease in children characterized by dermatitis and pruritus. MicroRNAs (miRNAs) have been shown as great potential biomarkers for disease fingerprints to predict prognostics. We aimed to identify miRNA signature from serum and urine for the prognosis of AD patient by genome-wide miRNA profiling analysis. Urine from 3 children with AD and 3 healthy children were collected
Project description:In order to analyze the regulatory effects of UII and GPR14 on gene transcription in Mc903-induced atopic dermatitis skin, ear skin collected from MC903 chronic itch mouse model on day 13 was used for in-depth analysis and sequencing of skin gene expression. The effect of GSK1562590 on the expression of pruritus and inflammatory factors in dermatitis was detected by RNA-seq.