Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of CerS4 deletion in murine epidermis on proteome and lipidome

ABSTRACT: Epidermal deletion of the lipid modifying enzyme CerS4 causes epidermal barrier impairments associated with human skin diseases. Proteomes of Wt newborn and P47 mice were compared in order to identify molecular differences between barrier formation and maintenance. Proteomes of epidermal splits from Ctr and CerS4epi-/- at different ages (P21, P33, P47) were compared, to identify the effect of CerS4 on barrier maintenance.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skin

SUBMITTER: Frederik Tellkamp

LAB HEAD: Carien M. Niessen

PROVIDER: PXD012220 | Pride | 2020-02-27

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Publications

Murine Epidermal Ceramide Synthase 4 Is a Key Regulator of Skin Barrier Homeostasis.

Peters Franziska F Tellkamp Frederik F Brodesser Susanne S Wachsmuth Emmi E Tosetti Bettina B Karow Ulrike U Bloch Wilhelm W Utermöhlen Olaf O Krönke Martin M Niessen Carien M CM

The Journal of investigative dermatology 20200222 10

Epidermal barrier dysfunction is associated with a wide range of highly prevalent inflammatory skin diseases. However, the molecular processes that drive epidermal barrier maintenance are still largely unknown. Here, using quantitative proteomics, lipidomics, and mouse genetics, we characterize epidermal barrier maintenance versus a newly established barrier and functionally identify differential ceramide synthase 4 protein expression as one key difference. We show that epidermal loss of ceramid ...[more]

PMID: 32092351

Similar Datasets

Genome-wide analysis of gene expression in Krt1+/+ versus Krt1-/- epidermis and full-thickness skin.

Project description:Keratin 1 (KRT1) and its heterodimer partner keratin 10 (KRT10) constitute the intermediate filament cytoskeleton of suprabasal skin keratinocytes. They participate in formation of the epidermal barrier, which protects against dehydration and inflammation. Mutations in KRT1 cause keratinopathic ichthyosis with erythema, recurrent inflammation, and barrier defects. Here, we show that genetic deletion of Krt1 in mice causes a defective inside-out epidermal barrier, pre- and postnatal increases in Mrp8/Mrp14, interleukin (IL) 18, IL-33, and thymic stromal lymphopoietin (TSLP) in skin extracts, and systemic release of IL-18 into newborn serum. Perinatal lethality was partially rescued by treatment with glucocorticoids to promote barrier repair or with IL- 18-blocking antibodies in utero. In human keratinocytes, IL-18 release was cellautonomous and caspase-1-dependent, indicating KRT1-dependent inflammasome activation. Our data reveal a novl function of KRT1 in controlling inflammasome activity and stimulating barrier formation, thereby integrating the keratin cytoskeleton into the epidermal immune response. In view of their widespread expression, keratins merit investigation of their functions in inflammatory conditions, including asthma and inflammatory bowel disorders. Total RNA was obtained from epidermis or full-thickness skin of Krt1+/+ and Krt1-/- mice (C57BL/6 background) at P0 (newborn).

2012-12-01 | E-GEOD-32951 | biostudies-arrayexpress

Genome-wide analysis of gene expression in Krt1+/+ versus Krt1-/- epidermis and full-thickness skin.

2012-12-01 | GSE32951 | GEO

Gene expression profiling of IR-/-, IGF-1R-/- (dKO) newborn epidermis.

Project description:Analysis of newborn mouse epidermis lacking the expression of Insulin receptor (IR) and Insulin like growth factor 1 receptor (IGF-1R). Results show that IR/IGF-1R signalling control epidermal morphogenesis. RNA was isolated from newborn mouse epidermis.Gene expression profiling was on on Affymetrix 430-2.0 platform.

2013-05-18 | E-GEOD-47065 | biostudies-arrayexpress

Gene expression profiling of IR-/-, IGF-1R-/- (dKO) newborn epidermis.

2013-05-18 | GSE47065 | 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

Atopic dermatitis epidermis PCT-DIA

Project description:Atopic Dermatitis (AD) is the most common inflammatory skin disease and characterized by a deficient epidermal barrier and cutaneous inflammation. Genetic studies suggest a key role of keratinocytes in AD pathogenesis, but the alterations in the proteome that occur in the entire epidermis have not been defined. Employing a pressure-cycling technology-data-independent acquisition (PCT-DIA) approach, we performed quantitative proteomics of epidermis from healthy volunteers and lesional and non-lesional skin of AD patients. Results were validated by targeted proteomics using parallel reaction monitoring mass spectrometry or by immunofluorescence staining. The identified proteins reflect the strong inflammation in lesional skin and the defect in keratinocyte differentiation and epidermal stratification. Most importantly, they reveal impaired activation of the NRF2-antioxidant pathway and reduced abundance of mitochondrial proteins involved in key metabolic pathways in the epidermis. These results provide insight into the molecular alterations in the epidermis of AD patients and identify novel targets for pharmaceutical intervention.

2022-10-04 | PXD025431 | Pride

Expression data from mouse adult epidermis in response to physical or immune mediated damage

2014-10-01 | GSE59384 | GEO

LincRNA-p21 Blocks Somatic Cell Reprogramming by Sustaining H3K9me3 and CpG Methylation at Pluripotent Gene Promoters

Project description:Through expression profiling and functional screening we have identified the large intergenic non-coding RNA p21 (lincRNA-p21) as a barrier for reprogramming. LincRNA-p21 is induced by p53 but contrary to its role in the DNA damage response it does not promote apoptosis or cell senescence in reprogramming. Instead, lincRNA-p21 associates with the H3K9 methyltransferase Setdb1 and the maintenance DNA methyltransferase Dnmt1 in separate complexes that are facilitated by the RNA binding protein hnRNP-K.

2014-12-29 | GSE57967 | GEO

Analysis of chromatin accessibility in human epidermis identifies putative barrier dysfunction-sensing enhancers

Project description:To identify putative gene regulatory regions that respond to epidermal injury, we mapped chromatin dynamics in a stratified human epidermis during barrier maturation and disruption. Engineered skin substitutes (ESS) cultured at the air-liquid interface were used as a model of developing human epidermis with incomplete barrier formation. The epidermal barrier stabilized following engraftment onto immunocompromised mice, and was compromised again upon injury. Modified formaldehyde-assisted isolation of regulatory elements (FAIRE) was used to identify accessible genomic regions characteristic of monolayer keratinocytes, ESS in vitro, grafted ESS, and tape-stripped ESS graft. We mapped differentiation- and maturation-associated changes in transcription factor binding sites enriched at each stage and observed overrepresentation of AP-1 gene family motifs in barrier- deficient samples. Transcription of TSLP, an important effector of immunological memory in response to allergen exposure, was dramatically elevated in our barrier-deficient samples. We identified dynamic DNA elements that correlated with TSLP induction and may contain enhancers that regulate TSLP. Two dynamic regions were located near the TSLP promoter and overlapped with allergy-associated SNPs rs17551370 and rs2289877, strongly implicating these loci in the regulation of TSLP expression in allergic disease. Additional dynamic chromatin regions ~250kb upstream of the TSLP promoter were found to be in high linkage disequilibrium with allergic disease SNPs. Taken together, these results define dynamic chromatin accessibility changes during epidermal development and dysfunction.

2017-08-28 | GSE101835 | GEO

Expression data from autophagy-deficient keratinocytes and normal keratinocytes

Project description:There is increasing evidence that autophagy contributes to the epidermal differentiation; however, the role of autophagy in epidermal tight junction (TJ) barrier remains unclear. To evaluate the role of autophagy in the maintenance of skin TJ barrier, we knocked out autophagy in human primary keratinocytes by infecting cells with autophagy-related gene 3 (Atg3) C264S mutant adenovirus.

2022-07-14 | GSE183921 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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