Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Laser capture microdissection followed by next-generation sequencing identifies disease-related microRNAs in psoriatic skin that mirror the systemic psoriatic miRNome

ABSTRACT: Psoriasis is a systemic disease with cutaneous manifestations. MicroRNAs (miRNAs) are non-coding RNA molecules that are differentially expressed in psoriatic skin, however; only few miRNAs have been localized to specific cells or regions of psoriatic lesions. We used laser capture microdissection (LCM) and next-generation sequencing to study the specific miRNA expression profiles in the epidermis (Epi) and dermal inflammatory aggregates (RD/ICs) of psoriatic skin. We identified 24 deregulated miRNAs in the Epi and 37 deregulated miRNAs in the RD/ICs of lesional psoriatic skin compared with non-lesional psoriatic skin (FCH>2, FDR<0.05). Interestingly, 9 of the 37 miRNAs, including miR-193b and miR-223 that have recently been described as deregulated in circulating peripheral blood mononuclear cells (PBMCs) from patients with psoriasis. Using flow cytometry and qRT-PCR, miR-193b and miR-223 were found to be expressed in Th17 cells. In conclusion, we demonstrate that LCM combined with small RNA sequencing provides a robust strategy to explore the global miRNA expression in the epidermal and dermal compartments of psoriatic skin. Furthermore, our results indicate that the altered local miRNA changes seen in the RD/ICs is reflected in the circulating immune cells, altogether emphasizing that miRNAs may contribute to a systemic component in the pathogenesis of psoriasis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE57012 | GEO | 2015/04/01

SECONDARY ACCESSION(S): PRJNA245208

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Laser capture microdissection followed by next-generation sequencing identifies disease-related microRNAs in psoriatic skin that mirror the systemic psoriatic miRNome

Project description:Psoriasis is a systemic disease with cutaneous manifestations. MicroRNAs (miRNAs) are non-coding RNA molecules that are differentially expressed in psoriatic skin, however; only few miRNAs have been localized to specific cells or regions of psoriatic lesions. We used laser capture microdissection (LCM) and next-generation sequencing to study the specific miRNA expression profiles in the epidermis (Epi) and dermal inflammatory aggregates (RD/ICs) of psoriatic skin. We identified 24 deregulated miRNAs in the Epi and 37 deregulated miRNAs in the RD/ICs of lesional psoriatic skin compared with non-lesional psoriatic skin (FCH>2, FDR<0.05). Interestingly, 9 of the 37 miRNAs, including miR-193b and miR-223 that have recently been described as deregulated in circulating peripheral blood mononuclear cells (PBMCs) from patients with psoriasis. Using flow cytometry and qRT-PCR, miR-193b and miR-223 were found to be expressed in Th17 cells. In conclusion, we demonstrate that LCM combined with small RNA sequencing provides a robust strategy to explore the global miRNA expression in the epidermal and dermal compartments of psoriatic skin. Furthermore, our results indicate that the altered local miRNA changes seen in the RD/ICs is reflected in the circulating immune cells, altogether emphasizing that miRNAs may contribute to a systemic component in the pathogenesis of psoriasis. Examination of the global miRNA expression in epidermis (Epi) and dermis (RD/ICs) of paired (non-lesional vs. lesional) psoriatic skin using a combination of laser-capture microdissection and barcoded small RNA sequencing

2015-04-01 | E-GEOD-57012 | biostudies-arrayexpress

Small RNA sequencing in normal and psoriatic skin

Project description:We report the application of Illumina small RNA sequencing to normal human skin, as well as uninvolved and involved psoriatic skin. By obtaining over 600 million qualified reads from 20 healthy controls and 47 psoriasis biopsies (uninvolved/involved), we have generated a complete small RNA profile in normal and diseased human skin, with particular emphasis on miRNAs. We report the discovery of 284 putative novel miRNAs as well as 98 differentially expressed miRNAs in psoriatic skin. miRNA discovery and expression profiling in 67 normal and psoriatic human skin biopsies

2011-08-19 | E-GEOD-31037 | biostudies-arrayexpress

Tissue-engineered human psoriatic skin as an in vitro model to study the impact of cytokines

Project description:Psoriasis is a chronic inflammatory disease of the skin for which no cure has emerged. Its complex etiology requires the development of an in vitro model that appropriately recapitulates the physiopathology of this disease. In this study, we exploited the self-assembly method in order to develop a new tissue-engineered model of psoriatic skin substitutes. To circumvent the addition of immune cells, we supplemented the reconstructed psoriatic substitutes with a cocktail of four cytokines, TNF-α, IL-1α, IL-6 and IL-17, and monitored their impact on global gene expression by DNA microarray. The cytokines-supplemented substitutes have a more irregular epidermis, with protuberances and much thinner areas. Most interestingly, gene profiling on microarrays identified several genes reported as being deregulated psoriasis skin in vivo. Indeed, expression of the S100A12, IL8, DEFB4A and KYNU genes increased dramatically compared to their level in normal skin substitutes (P <0.005 to <0.05). In addition, the ACSBG1 gene, reported to be repressed in psoriasis, was also repressed in the cytokines-supplemented psoriatic substitutes compared to the controls (P <0.005). The product encoded by the genes deregulated in the cytokines-supplemented substitutes belong to biological pathways, such as the inflammatory and the immune responses, that are similarly altered in psoriasis in vivo. In conclusion, addition of cytokines to involved psoriatic substitutes alters the transcriptome of these cells in a manner similar to that observed with psoriasis in vivo. The addition of this pro-inflammatory cocktail, comparable cytokine in vivo psoriasis, prepares us for the next step: the characterization of the model once added immune cells. Tissue-engineered psoriatic human skin (TEPHS) cultivated with (number of replicates: 3) or without (number of replicates: 3) Cytokines (IL-17a, IL-6, IL1a, TNF-a).

2015-04-11 | E-GEOD-67762 | biostudies-arrayexpress

Small RNA sequencing in normal and psoriatic skin

2011-08-19 | GSE31037 | GEO

Dissecting the miRNome of psoriatic keratinocytes

Project description:Purpose: The purpose of this study was to identify the miRNome of keratinocytes in psoriasis Method: We performed next-generation sequencing for small RNAs from the RNA samples obtained from keratinocytes from psoriasis lesional, non-lesional and healthy skin. Next, we removed adapters and the low quality tags from the sequencing data and clean reads were mapped and aligned to known miRNAs sequences (miRBase 21). Novel miRNA transcripts were predicted based on the length (22-25 nucleotide) and secondary structure (precursor analysis) using MIREAP and mapped to the human genome. Data were normalized (transcripts per million, TPM) and analysed using Bioconductor-EdgeR. Group comparisons (lesional vs. healthy, lesional vs. non lesional and non-lesional vs. healthy) were performed. MiRNAs with <10% FDR, fold change >1.4 (1 TPM at least in one of the groups and expressed in half of the samples in any group) were considered statistically significant. Results: Robust expression of 411 known and 30 novel miRNAs (TPM > 1 in >50% of the samples in at least one of the groups) was detected in our samples. Using EdgeR we identified 104 miRNAs with significantly altered level (fold change > 1.4, FDR < 0.1) between healthy and psoriatic keratinocytes (P vs H). While, pair-wise comparison of miRNA expression in keratinocytes from non-lesional and lesional psoriasis skin (P vs. N) identified 87 deregulated miRNAs. Comparison of the miRNome of keratinocytes from non-lesional skin of psoriasis patients to healthy keratinocytes (N vs. H) identified 7 differentially expressed miRNAs. Conclusion: Here, for the first time we show the keratinocyte miRNome in psoriasis which may serve as the basis for future functional studies of miRNAs deregulated in keratinocytes in psoriasis.

2019-07-23 | GSE129373 | GEO

Hsa-miR-31-5p controls a metabolic switch in psoriatic keratinocytes that identifies therapeutic intervention

Project description:Next to genetic alterations, it is being recognized that the cellular environment also acts as a major determinant in onset and progression of disease. In cases where different cell types contribute to the final disease outcome, this imposes environmental challenges as different cell types likely differ in their extracellular dependencies. A number of skin diseases, including psoriasis is characterized by a combination of keratinocyte hyperproliferation and immune cell activation. Activation of immune cells involves increased glucose consumption thereby intrinsicly limiting glucose availability for other cell types. Thus, these type of skin diseases require metabolic adaptations that enable coexistence between hyperproliferative keratinocytes and activated immune cells in a nutrient-limited environment. Hsa-microRNA-31-5p (miR-31) is highly expressed in keratinocytes within the psoriatic skin. Here we show that miR-31 expression in keratinocytes is induced by limited glucose availability and enables increased survival of keratinocytes under limiting glucose conditions, by increasing glutamine metabolism. In addition, miR-31 induced glutamine metabolism results in secretion of specific metabolites (aspartate and glutamate) but also secretion of immuno-modulatory factors. We show that this miR-31-induced secretory phenotype is sufficient to induce Th17 cell differentiation, a hallmark of psoriasis. Inhibition of glutaminase (GLS) using CB-839 impedes miR31-induced metabolic rewiring and secretion of immuno-modulatory factors. Concordantly, pharmacological targeting of GLS alleviated psoriasis pathology in a mouse model of psoriasis. Together our data illustrate an emerging concept of metabolic interaction across cell compartments that characterizes disease development, which can be employed to design effective treatment options for disease, as shown here for psoriasis.

2023-02-06 | PXD029030 | Pride

MicroRNA profiling of psoriatic skin identifies 11 miRNAs associated with disease severity

Project description:MicroRNAs (miRNAs) are small non-coding RNAs that have emerged as central regulators of gene expression and powerful biomarkers of disease. Much is yet unknown about their role in psoriasis pathology. To globally characterize the miRNAome of psoriatic skin, skin biopsies were collected from psoriatic cases (n = 75) and non-psoriatic controls (n = 57) and RNA sequenced. Count data was meta-analyzed with a previously published dataset (cases, n = 24, controls, n = 20), increasing the number of psoriatic cases four-fold from previously published studies. Differential gene expression analyses were performed comparing lesional psoriatic (PP), non-lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell-specific analyses were performed. Across all contrasts, we identified 439 significantly differentially expressed miRNAs (DEMs), of which 127 were novel for psoriasis and 11 were related to disease severity. Meta-analyses identified 20 DEMs between PN and NN, suggesting an inherent change in the constitution of all skin in psoriasis. By integrating the miRNA transcriptome with mRNA target interactions, we identified several functionally enriched terms, including ‘thyroid hormone signaling’, ‘insulin resistance’ and various infectious diseases. Cell specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells. This study provides the most comprehensive overview of the miRNAome in psoriatic skin to date and identifies a miRNA signature related to psoriasis severity. Our results may represent molecular links between psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify biomarkers and treatment targets.

2021-10-31 | GSE174763 | GEO

Global methylation analysis of psoriatic (involved and uninvolved) and control skin

Project description:Psoriasis is a chronic inflammatory immune-mediated disorder affecting the skin and other organs including joints. Over 1,300 transcripts are altered in psoriatic involved skin compared to normal skin. Global epigenetic profiles of psoriatic skin have not been described. Here we describe the first genome-wide study of altered CpG methylation in psoriatic skin. We determined the methylation levels at 27,578 CpG sites in skin samples from individuals with psoriasis (12 involved, 8 uninvolved) and 10 unaffected individuals. CpG methylation of involved skin differed from normal skin at 1,108 sites. Twelve mapped to the epidermal differentiation complex, upstream or within genes that are highly up-regulated in psoriasis. Hierarchical clustering of 50 of the top differentially methylated (DM) sites separated psoriatic from normal skin samples. CpG sites where methylation was correlated with gene expression are reported. Sites with inverse correlations between methylation and nearby gene expression include those of KYNU, OAS2, S100A12, and SERPINB3, whose strong transcriptional up-regulation are important discriminators of psoriasis. We observed intrinsic epigenetic differences in uninvolved skin. Pyrosequencing of bisulfite-treated DNA from skin biopsies at three DM loci confirmed earlier findings and revealed a reversion of methylation levels towards the non-psoriatic state after one month of anti-TNF-a therapy. Control n=8 (NN), psoriasis involved n = 19 (PP), psoriasis uninvolved n=8 (PN). Hybridized to Illumina Human 27k methylation array. Paired samples are as follows: PN1 and PP1 PN2 and PP2 PN3 and PP3 PN4 and PP4 PN5 and PP5 PN6 and PP6 PN7 and PP7 PN8 and PP8

2011-11-11 | E-GEOD-31835 | biostudies-arrayexpress

Tissue-engineered human psoriatic skin as an in vitro model to study the impact of cytokines

2015-04-11 | GSE67762 | GEO

IL-17 mediated downregulation of miR-101 facilitates expression of EZH2 to promote epidermal hyperplasia in psoriasis

Project description:Epidermal hyperplasia, a characteristic feature of psoriatic skin lesions, is epigenetically driven by Enhancer of Zeste homolog 2 (EZH2). EZH2 and EZH2-mediated trimethylation of histone H3 lysine 27 (H3K27me3) are both abnormally upregulated in psoriatic lesions. To identify microRNAs that could potentially target these epigenetic regulators we profiled miRNAs from psoriatic lesional skin in comparison with healthy skin. Analysis of the differentially expressed miRNAs revealed miR-101, as one of the most significant miRNA, consistently downregulated in psoriatic lesions compared to the healthy skin. A clear inverse correlation in the expression of miR-101 versus EZH2 was apparent in normal skin versus psoriatic lesional skin indicating that EZH2 is a potential target of miR-101, which was further confirmed by luciferase assay. Investigating the upstream effectors of the miR-101- EZH2 pathway in psoriasis, we identified the pro-inflammatory cytokine IL-17 as regulator of miR-101 expression. Here we propose a model, depicting a pathway triggered by IL-17 – mediated modulation of miR-101 expression, which in turn elicit sustained expression of EZH2, leading to enhanced keratinocyte proliferation and epidermal hyperplasia in psoriasis. Taken together, this indicates that miR-101 is a potential therapeutic target to alleviate the downstream effects of IL-17 mediated epidermal hyperplasia in psoriasis.

2023-09-19 | GSE220586 | GEO