Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Proteomic analysis of a filaggrin-deficient skin organoid model shows evidence of increased translation, keratinocyte-immune crosstalk and disordered axon guidance

ABSTRACT: Atopic eczema is an itchy inflammatory disorder characterised by skin barrier dysfunction. Loss-of-function mutations in the gene encoding filaggrin (FLG) are a major risk factor, but the mechanisms by which filaggrin haploinsufficiency leads to atopic inflammation remain incompletely understood. Skin as an organ which can be modelled using primary cells in vitro provides the opportunity for selected genetic effects to be investigated in detail.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Keratinocyte, Skin

DISEASE(S): Eczema

SUBMITTER: Sara ten Have

LAB HEAD: Sara Brown

PROVIDER: PXD014875 | Pride | 2019-08-14

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	PT7542-1.raw	Raw
	PT7542-10.raw	Raw
	PT7542-11.raw	Raw
	PT7542-12.raw	Raw
	PT7542-13.raw	Raw

Items per page:

1 - 5 of 99

Publications

Functional and proteomic analysis of a full thickness filaggrin-deficient skin organoid model.

Elias Martina S MS Wright Sheila C SC Nicholson William V WV Morrison Kimberley D KD Prescott Alan R AR Ten Have Sara S Whitfield Phillip D PD Lamond Angus I AI Brown Sara J SJ

Wellcome open research 20191126

Background: Atopic eczema is an itchy inflammatory disorder characterised by skin barrier dysfunction. Loss-of-function mutations in the gene encoding filaggrin ( FLG) are a major risk factor, but the mechanisms by which filaggrin haploinsufficiency leads to atopic inflammation remain incompletely understood. Skin as an organ that can be modelled using primary cells in vitro provides the opportunity for selected genetic effects to be investigated in detail. Methods: P ...[more]

PMID: 31641698

Similar Datasets

Human gene 1.0 ST AD/IV Gene expression

Project description:Comparison of gene expression in atopic dermatitis (AD) and ichthyosis vulgaris (IV) patients skin compared to healthy control skin depending on filaggrin(FLG) genotype

2011-10-01 | E-MTAB-768 | biostudies-arrayexpress

EMSY expression affects multiple components of skin barrier with relevance to atopic dermatitis

Project description:Atopic dermatitis (AD) is a heritable inflammatory disease, characterised by skin barrier dysfunction. Genome-wide association studies (GWAS) have identified molecular targets with relevance for drug development, but the strongest genetic association, FLG, has not yet been successfully targeted in atopic disease. An AD-associated locus on chromosome 11q13.5 lies between two genes - EMSY and LRRC32 - but the functional mechanisms leading to AD are unclear. We applied a combination of genomic and molecular analytical techniques followed up in patient biopsies, to investigate pathomechanisms at this GWAS locus. Chromosome conformation capture data in keratinocytes shows interaction of the intergenic region in threedimensional space with EMSY. siRNA-mediated knockdown of EMSY in skin organoid culture leads to enhanced development of barrier function, measured by water evaporation and dye penetration. Global proteomic analysis of skin organoids with EMSY knockdown shows increased expression of structural and functional proteins, confirmed by histological and ultrastructural features. Lipid analysis shows an increase in ceramides known to be reduced in AD. Conversely, over-expression of EMSY in primary human keratinocytes leads to a reduction in biomarkers of barrier formation. Finally, skin biopsy samples from patients with AD show greater EMSY staining in the nucleus, consistent with increased functional effect of this DNAbinding protein. Together our findings demonstrate an important role for EMSY in transcriptional regulation and skin barrier formation, supporting EMSY inhibition as a therapeutic approach for AD.

2019-06-24 | PXD014088 | Pride

Gene expression profiling of filaggrin-insufficient keratinocytes exposed to inflammatory mediators and allergens

Project description:Loss-of-function mutations in the filaggrin gene are heavily associated with the incidence and severity of atopic dermatitis. Moreover, filaggrin insufficiency in epidermal keratinocytes can lead to persistent allergic inflammation and an associated immune response suggesting a role for this protein in regulation of immunity. Here, we investigate how filaggrin insufficiency affects the gene expression pattern in a filaggrin-insufficient (shFLG) keratinocyte cell line HaCaT in response to stimulation with various inflammatory mediators and allergens.

2022-05-20 | GSE203409 | GEO

Alteration of the whole skin gene expression as a result of Flg deficiency

Project description:Defects of filaggrin (FLG) compromise epidermal barrier function and represent an important known genetic risk factor for atopic dermatitis (AD), but also for systemic atopy, including allergic sensitization and asthma. A loss of epidermal barrier integrity can provide a significant stress for the cells in both the epidermis as well as the underlying dermal layer of the skin, either due to the increased moisture evaporation from the skin or increased penetration of the antigens and microflora into the lower layers. This analysis was therefore designed to understand the effect of this loss of barrier integrity on the total skin transcriptional profile.

2021-05-01 | GSE164623 | GEO

Alteration of keratinocyte gene expression as a result of Flg deficiency

Project description:Defects of filaggrin (FLG) compromise epidermal barrier function and represent an important known genetic risk factor for atopic dermatitis (AD), but also for systemic atopy, including allergic sensitization and asthma. A loss of epidermal barrier integrity can provide a significant stress for the keratinocytes in the skin, either due to the increased moisture evaporation from the skin or increased penetration of the antigens and microflora into the lower epidermal layers. To understand the effect of this loss of barrier integrity on keratinocyte function our aim is to analyze the alterations in the transcriptional profile of keratinocytes from Flg-deficient mice.

2021-01-01 | GSE158028 | GEO

Disrupting TSLP - TSLP receptor interactions via small molecule inhibitors yields a novel and efficient treatment option for atopic diseases

Project description:Thymic stromal lymphopoietin (TSLP) is a key player in the pathogenesis of atopic diseases. Its pathophysiological relevance has sparked great interest in therapeutically targeting TSLP. Yet, so far, no small-mo lecule TSLP inhibitors exist due to the challenging nature of disrupting the protein-protein interaction between TSLP and its receptor. Here, we report the development of small-molecule TSLP receptor inhibitors using structure- based virtual screening and docking of >1,000,000 compounds followed by iterative chemical synthesis. BP79 emerged as our lead compound that effectively abrogates TSLP-triggered cytokine release at low micromolar concentrations. Topical application of BP79 yields efficient skin absorption followed by significant downregulation of atopy-relevant proinflammatory cytokines in immunocompetent skin disease models. For further analysis, we developed a human atopic disease drug discovery platform using microfluidic multi-organ chips. Here, topical application of BP79 onto atopic-like skin disease models that were co -cultivated with lung models in the presence of Th2 cells effectively suppressed immune cell infiltration and key atopy mediators including IL-13, IL-4, TSLP, and periostin, while upregulating skin barrier prote ins such as filaggrin. RNA-Seq analysis corroborated these findings and also indicated protective downstream effects on the lung epithelium. To the best of our knowledge, this represents the first report of a po tent and safe small molecule TSLPR inhibitor which has the potential to expand the therapeutic and preventive options in atopic diseases. Further, it serves as a starting point for further developments in target ing TSLP as a central player of inflammation.

2024-05-17 | GSE264457 | GEO

Mapping the Periostin splice isoforms in atopic dermatitis and an in vitro asthma model – A multi-platform analysis using mass spectrometry and RT-qPCR

Project description:Periostin is a matricellular protein known to be alternatively spliced to produce isoforms with a molecular weight of 78-91 kDa. In the extracellular matrix, periostin attach to cell surfaces and induce signaling via integrin-binding and participates in fibrillogenesis to organize collagen in the extracellular space. In the atopic diseases atopic dermatitis and asthma, periostin is known to participate in driving the disease-causing type 2 inflammation. The periostin isoforms expressed in these diseases and the implication of the alternative splicing events are unknown. Here we present two universal assays to map the expression of periostin isoforms on both the transcriptional (RT-qPCR) and translational (PRM-based mass spectrometry) level. We use these assays to study the splice profile of periostin in atopic dermatitis lesions from patients in active treatment vs. normal skin and in in vitro models of atopic dermatitis and asthma. All isoforms expect isoform 3 show decreased expression at the transcriptional level in AD lesions from patients treated with corticosteroids compared to normal skin. The isoforms display an elevated amount at the translational level indicating a delayed response in periostin level during treatment. Expression of the isoforms were upregulated in the in vitro models of atopic dermatitis and asthma at both the transcriptional and translational level with isoform 3 and 5 displaying the highest level of overexpression. Interestingly, the often overlooked isoform 9 and 10 behaved opposite to the other isoforms as they were equally or even less abundant in the disease models compared to the control, and they were identified in the normal skin samples but not in atopic dermatitis lesions. With the assays and findings presented in the publication connected to this dataset we can take further steps in mapping and understanding the role of periostin isoforms.

2024-07-08 | PXD045287 | Pride

Proteomic analysis of filaggrin insufficient keratinocytes and secreted exosomes.

Project description:Filaggrin (FLG) is a key structural protein expressed in epidermal keratinocytes. Mutations in the filaggrin gene (FLG) are strongly linked to atopic dermatitis (AD) and allergic inflammation occurring later in life at distant body locations in AD patients. Keratinocytes secrete exosomes, small, lipid-rich membrane vesicles to communicate with distant cells, including within the immune system. The FLG gene was silenced in the HaCaT keratinocyte cell line by shRNA delivered using a lentiviral vector. HaCaT cells transduced with scrambled shRNA were used as a control.

2022-08-12 | PXD026859 | Pride

Gastric gene expression of patients with type-1 gastric neuroendocrine tumours

Project description:Differentially expressed genes in the stomachs of type-1 gastric neuroendocrine tumour (NET) patients before, during and after treatment with netazepide (YF476)

2018-12-30 | E-MTAB-6473 | biostudies-arrayexpress

Proteome and phospholipidome interrelationship of synovial fluid-derived extracellular vesicles in Equine osteoarthritis: An exploratory ‘multi-omic’ study

Project description:Osteoarthritis (OA) causes persistent joint deterioration, severe morbidity, and reduced mobility in both humans and horses. Extracellular vesicles (EVs) are key players in cell-to-cell communication and are thus ideal for biomarker discovery. Here, we used a unique multi-omics strategy to find possible EV biomarkers from the synovial fluid of healthy horses compared to naturally occurring OA and advanced OA. We discovered that SF-EVs’ proteome and phospholipidome are correlated. Furthermore, we found that the quantity of EVs present in SF was unaffected by OA. We discovered crucial signalling pathways involving integrins (p=2.72x10-24), the actin cytoskeleton (p=3.88x10-32), Rho family GTPases (p=1.24x10-19), and the clathrin-mediated endocytosis pathway (p=1.30x10-24). Specifically, the advanced OA group’s immunological response (macrophage binding and interaction) was upregulated. These findings are suggestive that the membrane and protein cargo of SF-EVs are altered in response to OA pathology and may be used as biomarkers of disease. Consequently, SF-EVs could have the potential to be employed in the future to help with OA stratification and prognosis. In addition, this study provides a framework for future research using a larger cohort.

2024-05-24 | PXD042765 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data