Gene expression profile of epidermis from psoriasis lesions and healthy controls
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE166388 | GEO | 2021/02/09
REPOSITORIES: GEO
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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
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.
2013-12-10 | GSE50790 | GEO
Project description:Gene expression profile of epidermis from psoriasis lesions and healthy controls
| PRJNA700654 | ENA
Project description:The efficacy of monoclonal antibodies against either interleukin (IL)-17 or the IL-17 receptor in psoriasis therapy provides strong evidence that IL-17 is the major inflammatory mediation in this disease. However, how IL-17 induces epidermal hyperplasia in psoriasis remains largely unknown. Here, we show that IL-17 actives NF-kB in keratinocytes and initiates the NF-kB-dependent transcription of microRNA-31 (miR-31), one of the most abundant microRNAs in the epidermis of lesional skin of psoriasis and two related mouse models. Similar to IL-17 deficiency (IL-17-/-), knocking out miR-31 (miR-31-/-) or targeting it by antagomir-31 prevents keratinocytes Ki67 expression and inhibits acanthosis and dermal inflammation in psoriasis mouse model. Moreover, PPP6c, a negative regulator restricting G0/G1 to G2/M phase progression in the cell cycle, is diminished in human psoriatic epidermis and is directly targeted by miR-31. Inhibition of ppp6c is functionally important for the biological effects of miR-31 in the development of epidermal hyperplasia. Thus, our data define IL-17-inducede miR-31 and its target ppp6c as critical factors for hyperproliferative epidermis in psoriasis. Epidermis samples from affected ears derived from 3 CD18hypo PL/J mice (DIS) or normal ears derived from 3 CD18hypo C57BL/6J mice(2128) were used for RNA extraction and hybridization on Affymetrix microarrays. We sought to compare miRNA expression of normal skin from control and lesional skin.
2013-12-31 | E-GEOD-50099 | biostudies-arrayexpress
Project description:The immunopathogenesis of psoriasis, a common chronic inflammatory disease of the skin, is incompletely understood. Here we demonstrate, using a combination of single cell and spatial RNA sequencing, IL-36 dependent amplification of IL-17A and TNF inflammatory responses in the absence of neutrophil proteases, which primarily occurred within the supraspinous layer of the psoriatic epidermis. We further show that a subset of SFRP2+ fibroblasts in psoriasis contribute to amplification of the immune network through transition to a pro-inflammatory state. The SFRP2+ fibroblast communication network involves production of CCL13, CCL19 and CXCL12, connected by ligand-receptor interactions to other spatially proximate cell types: CCR2+ myeloid cells, CCR7+ LAMP3+ dendritic cells, and CXCR4 expressed on both CD8+ Tc17 cells and keratinocytes, respectively. The SFRP2+ fibroblasts also express cathepsin S, further amplifying inflammatory responses by activating IL-36G in keratinocytes. These data provide an unprecedented view of psoriasis pathogenesis, which expands our understanding of the critical cellular participants to include inflammatory fibroblasts and their cellular interactions.
2023-05-07 | GSE225475 | GEO
Project description:IL-20 cytokines are involved in the establishment of psoriasis, a common chronic skin inflammation epidemiologically associated with metabolic syndrome, but molecular mechanisms underlying their over-expression remain to be elucidated. We find that keratinocytes (KCs) expressed IL-20 and lymphocytes expressed IL-22 cytokines up-regulation occurs at post-transcriptional level with stabilization of their RNA messengers. Looking at psoriatic epidermis, we observe that the p38/MK2 pathway is not activated but that the RNA-binding protein (RBP) HuR re-localizes in keratinocytes cytoplasm, suggesting post-transcriptional regulation of numerous mRNAs. HuR ribonucleoprotein immunoprecipitations analyzed by high-throughput sequencing (RIP-Seq) identify potential pre-mature and mature RNA targets for uninvolved and involved skin and confirms that HuR activity is displaced from the nucleus to the cytoplasm. Numerous psoriasis up-regulated transcripts are HuR targets and HuR knockdown reduces expression of transcripts like beta-defensin-2, CXCL-10 or IL-2, suggesting an implication of HuR in pathophysiological processes such as morphological, immune and metabolic inflammatory responses. Finally, metabolic disorders affecting psoriatic keratinocytes are responsible for HuR cytoplasmic localization since a decreased activity of the cellular metabolic sensor AMPK, that is observed in human psoriatic epidermis, is sufficient to promote HuR cytosolic localization as well as IL-20 over-production both in human keratinocytes and in vivo in mouse epidermis where it then initiates psoriasis-like histological changes. These results may provide insights into molecular links between metabolism and post-transcriptional networks during chronic inflammation, as illustrated in psoriasis by mechanisms connecting AMPK, HuR and IL-20. Analysis of HuR-binding RNA in uninvolved versus involved psoriatic samples by RIP-Seq. Samples from five different patients were used for both uninvolved and involved skin. RIP-Seq was also made using a control IgG.
2015-09-08 | E-GEOD-50598 | biostudies-arrayexpress
Project description:The efficacy of monoclonal antibodies against either interleukin (IL)-17 or the IL-17 receptor in psoriasis therapy provides strong evidence that IL-17 is the major inflammatory mediation in this disease. However, how IL-17 induces epidermal hyperplasia in psoriasis remains largely unknown. Here, we show that IL-17 actives NF-kB in keratinocytes and initiates the NF-kB-dependent transcription of microRNA-31 (miR-31), one of the most abundant microRNAs in the epidermis of lesional skin of psoriasis and two related mouse models. Similar to IL-17 deficiency (IL-17-/-), knocking out miR-31 (miR-31-/-) or targeting it by antagomir-31 prevents keratinocytes Ki67 expression and inhibits acanthosis and dermal inflammation in psoriasis mouse model. Moreover, PPP6c, a negative regulator restricting G0/G1 to G2/M phase progression in the cell cycle, is diminished in human psoriatic epidermis and is directly targeted by miR-31. Inhibition of ppp6c is functionally important for the biological effects of miR-31 in the development of epidermal hyperplasia. Thus, our data define IL-17-inducede miR-31 and its target ppp6c as critical factors for hyperproliferative epidermis in psoriasis.
2013-12-31 | GSE50099 | GEO
Project description:IL-20 cytokines are involved in the establishment of psoriasis, a common chronic skin inflammation epidemiologically associated with metabolic syndrome, but molecular mechanisms underlying their over-expression remain to be elucidated. We find that keratinocytes (KCs) expressed IL-20 and lymphocytes expressed IL-22 cytokines up-regulation occurs at post-transcriptional level with stabilization of their RNA messengers. Looking at psoriatic epidermis, we observe that the p38/MK2 pathway is not activated but that the RNA-binding protein (RBP) HuR re-localizes in keratinocytes cytoplasm, suggesting post-transcriptional regulation of numerous mRNAs. HuR ribonucleoprotein immunoprecipitations analyzed by high-throughput sequencing (RIP-Seq) identify potential pre-mature and mature RNA targets for uninvolved and involved skin and confirms that HuR activity is displaced from the nucleus to the cytoplasm. Numerous psoriasis up-regulated transcripts are HuR targets and HuR knockdown reduces expression of transcripts like beta-defensin-2, CXCL-10 or IL-2, suggesting an implication of HuR in pathophysiological processes such as morphological, immune and metabolic inflammatory responses. Finally, metabolic disorders affecting psoriatic keratinocytes are responsible for HuR cytoplasmic localization since a decreased activity of the cellular metabolic sensor AMPK, that is observed in human psoriatic epidermis, is sufficient to promote HuR cytosolic localization as well as IL-20 over-production both in human keratinocytes and in vivo in mouse epidermis where it then initiates psoriasis-like histological changes. These results may provide insights into molecular links between metabolism and post-transcriptional networks during chronic inflammation, as illustrated in psoriasis by mechanisms connecting AMPK, HuR and IL-20.
2015-09-08 | GSE50598 | GEO
Project description:Herein we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n=3) were compared with littermate controls (n=3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average P = 0.0082; cystatin A, human orthologue); slc25a5 (average fold change of 46.2 and an average P = 0.0318); serpinb3b (average fold change of 35.6 and an average P = 0.0345; serpinB1, human orthologue); and kallikrein related peptidase 6 (average fold change of 4.7 and an average P = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, P < 0.0001), KLK6 (9.0-fold, P = 0.002), stefin A1 (7.3-fold; P < 0.001) and slc25A5 (1.5-fold; P = 0.05) using qRT-PCR on a second cohort of animals (n=8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; P < 0.05), 29,000-fold (stefinA1; P < 0.01), 322-fold (KLK6; P < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes vs. healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3.0-fold), KLK6 (5.8-fold) and serpinB1 (76-fold; all P < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover slc25a5, cystatin A, KLK6 and serpinB1 protein were all increased in lesional psoriasis skin compared to normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.
2014-10-30 | PXD001387 | Pride
Project description:Arp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis.We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistently, we unveiled that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocytes' shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis.
2017-11-23 | GSE107265 | GEO