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Intense THz pulses down-regulate genes associated with skin cancer and psoriasis: a new therapeutic avenue?

ABSTRACT: We show that exposure of artificial human skin tissue to intense, picosecond-duration THz pulses affects expression levels of numerous genes associated with non-melanoma skin cancers, psoriasis and atopic dermatitis. Genes affected by intense THz pulses include nearly half of the epidermal differentiation complex (EDC) members. EDC genes, which are mapped to the chromosomal human region 1q21, encode for proteins that partake in epidermal differentiation and are often overexpressed in conditions such as psoriasis and skin cancer. In nearly all the genes differentially expressed by exposure to intense THz pulses, the induced changes in transcription levels are opposite to disease-related changes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE48586 | GEO | 2013/07/09

SECONDARY ACCESSION(S): PRJNA210754

REPOSITORIES: GEO

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Intense THz pulses down-regulate genes associated with skin cancer and psoriasis: a new therapeutic avenue?

Project description:We show that exposure of artificial human skin tissue to intense, picosecond-duration THz pulses affects expression levels of numerous genes associated with non-melanoma skin cancers, psoriasis and atopic dermatitis. Genes affected by intense THz pulses include nearly half of the epidermal differentiation complex (EDC) members. EDC genes, which are mapped to the chromosomal human region 1q21, encode for proteins that partake in epidermal differentiation and are often overexpressed in conditions such as psoriasis and skin cancer. In nearly all the genes differentially expressed by exposure to intense THz pulses, the induced changes in transcription levels are opposite to disease-related changes. Total RNA from exposed artificial human skin tissues to picosecond-duration broadband (0.2–2.5 THz) THz pulses with 1 kHz repetition rate, 1/e2 spot-size diameter of 1.5 mm and pulse energies of either 1.0 ?J or 0.1 ?J. For comparison, we have exposed skin tissues to UVA pulses (400 nm, 0.1 ps, 0.024 ?J).

2013-07-09 | E-GEOD-48586 | biostudies-arrayexpress

Homo sapiens

Project description:Intense THz pulses down-regulate genes associated with skin cancer and psoriasis: a new therapeutic avenue?

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Ovol1 regulates psoriasis-like skin inflammation and epidermal hyperplasia

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

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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

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.

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Driving Intracellular Metal Ions of Human Induced Pluripotent Stem Cells with Intense Terahertz Pulses

Project description:Terahertz (THz) radiation has been exploited for biomedical applications for non-invasive manipulation of living cells. Here we describe an apparatus to apply high-field THz excitation on highly environmental sensitive human induced pluripotent stem cells (hiPSCs), and manipulate the gene expression networks associated with zinc-finger (ZNF) transcription factors.

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Driving Intracellular Metal Ions of Human Induced Pluripotent Stem Cells with Intense Terahertz Pulses

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Wound response in fs-THz-irradiated mouse skin

Project description:Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. However, the biological effect of THz radiation is not fully understood. Non-thermal effects of THz radiation were investigated by applying a femtosecond-terahertz (fs-THz) pulse to mouse skin. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly through NF?B1- and Smad3/4-mediated transcriptional activation. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of transforming growth factor-beta (TGF-?). These findings suggest that fs-THz radiation provokes a wound-like signal in skin with increased expression of TGF-? and activation of its downstream target genes, which perturbs the wound healing process in vivo. To identify non-thermally induced in vivo mode action of THz radiation, gene expression profile of fs-THz-irradiated skin (at post 24-hours after 1 hour exposure) was explored. Purified total RNAs from independent 3 mice of each sham and THz group were labeled and hybridized on the Mouse Gene 1.0 ST Array (Affymetrix, Santa Clara, CA), according to manufacturer's standard protocol. Statistically filtered THz-responsive genes were examined for possible interactions with other molecules, canonical signaling pathways, and bio-functions.

2013-02-26 | E-GEOD-44671 | biostudies-arrayexpress

Wound response in fs-THz-irradiated mouse skin

2013-02-26 | GSE44671 | GEO

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

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