IL-25 participates in keratinocyte-driven dermal matrix turnover and is reduced in Systemic Sclerosis epidermis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA706788 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Aberrant deposition of extracellular matrix (ECM) resulting in dermal fibrosis is a hallmark of systemic sclerosis (SSc). Evidence suggests that dysfunctional SSc keratinocytes may contribute to fibrosis by altering dermal homeostasis. Whether interleukin-25 (IL-25), an IL-17 family member involved in epithelial/mesenchymal/immune cell interplay takes part in skin fibrosis is unknown. Here we address the role of IL-25 in SSc skin fibrosis. Compared to healthy donor (HD), in SSc and scleroderma-like disorders the epidermis expressed significantly lower levels of IL-25. In epidermal equivalents, IL-25 regulated several molecular pathways related to wound healing and ECM remodeling. Compared to control conditioned medium (CM), the CM from IL-25-primed keratinocytes enhanced the production by fibroblasts of matrix metalloproteinase-1 (MMP-1), IL-6, IL-8 (p< 0.05), but not of type-I collagen (Col-I ) nor fibronectin. However, IL- 25 significantly reduced the production of Col-I when applied directly to fibroblasts. The activation of keratinocytes by IL-25 was receptor-dependent and evident after a very short incubation time (10 min), largely mediated by IL-1, suggesting enhanced and specific release of preformed mediators. These results show that IL-25 participates to skin homeostasis and its decreased expression in SSc may contribute to skin fibrosis by favoring ECM deposition over degradation.
2022-03-31 | GSE168312 | GEO
Project description:To characterize the global transcriptome of human keratinocyte stem cells (KSC) and keratinocyte progenitors (KP), primary basal keratinocyte subpopulations enriched in quiescent stem cells [Itg-α6bright / Trf-Rdim] or in cycling progenitors [Itg-α6bright / Trf-Rbright] were purified by flow cytometry from human skin samples. Sorted keratinocytes were then seeded in culture plates and maintained in culture medium overnight (15 hours), and genome-wide transcriptome analysis of these two subpopulations was directly performed, in order to globally maintain the initial phenotypes. After RNA preparation, gene profiling was performed using oligonucleotide microarrays (26068 probes). LOWESS normalisation was applied. Keywords: epidermis, keratinocyte stem cells, progenitors, transcriptome, stemness
2015-05-06 | GSE68583 | GEO
Project description:To characterize the global transcriptome of human keratinocyte stem cells (KSC) and keratinocyte progenitors (KP), primary basal keratinocyte subpopulations enriched in quiescent stem cells [Itg-?6bright / Trf-Rdim] or in cycling progenitors [Itg-?6bright / Trf-Rbright] were purified by flow cytometry from human skin samples. Sorted keratinocytes were then seeded in culture plates and maintained in culture medium overnight (15 hours), and genome-wide transcriptome analysis of these two subpopulations was directly performed, in order to globally maintain the initial phenotypes. After RNA preparation, gene profiling was performed using oligonucleotide microarrays (26068 probes). LOWESS normalisation was applied. Keywords: epidermis, keratinocyte stem cells, progenitors, transcriptome, stemness Dye-swap hybridization were performed. Slides were scanned with a Genepix 4000 microarray scanner (Axon Instruments, Molecular devices, Sunnyvale, CA). For each hybridized spot, the Cy3 and Cy5 fluorescence values were obtained by using Genepix Pro 4.0 software (Axon Instruments) and were saved as a result file
2015-05-06 | E-GEOD-68583 | biostudies-arrayexpress
Project description:Keratinocytes of the epidermis undergo massive remodeling of intracellular structures to enter the stratum corneum. This work investigates the degree to which autophagy participates in the remodeling by comparing corneocytes from the sole (foot pads) of wild type (WT, n=5, samples names NK70-74) to those from mice (EKO, n=6, samples names NK75-80) with epidermal keratinocyte-specific deletion of Autophagy-related gene 7 (Atg7). Sample NK81 is a blank. The cornified layer of the epidermis (stratum corneum) was sampled by tape-stripping from the soles of hind limbs and subjected to label-free proteomics as previously described (Karim et al. PLoS One 2023;18:e0283619). Among more than 170 proteins detected, 10 proteins were significantly increased in abundance when autophagy was suppressed. The autophagy-dependent alterations in the protein composition of corneocytes are less pronounced than those in hard cornified skin appendages. Since the proteome of the stratum corneum depends partly on autophagy in keratinocytes, it may be used for the detection of autophagy-dependent aberration of keratinocyte differentiation.
2024-07-16 | MSV000095353 | MassIVE
Project description:In epidermis, granular keratinocytes are responsible for the synthesis of a great number of proteins of high tissue-specificity, and required for the epidermal barrier establishment and the regulation of the desquamation process. This project aims at characterizing the physiopathological function of genes implicated in these processes, and in the short term, defining their expression level in the course of keratinocyte differentiation. Pangenomic oligonucleotide microarrays are used to compare their expression between two cell populations enriched in basal or granular keratinocytes (T1 and T4 fractions resp.), obtained by successive incubations in trypsin solution of six independent normal human epidermis samples. Real-time quantitative PCR experiments were further performed to ensure the validity of the profiling for each candidate gene identified from microarrays data, and results of this multitechnique approach will be the object of a forthcoming publication. These results will be the basis for a better understanding of dermatological hyperkeratotic pathologies. Within epidermis, keratinocytes achieve a differentiation program culminating in cornification, a programmed cell death required for the establishment of the barrier function. A complex genetic regulatory network underlies the numerous biochemical modifications taking place in the last living cells, the granular keratinocytes (GKs), but very few transcription factors specific from this process were identified. Here we describe a large-scale, multitechnique approach performed on cells purified from normal human epidermis, and mainly focused on identification of these regulators. We performed microarray experiments to compare gene expression in cell fractions enriched in granular or basal keratinocytes. These data, with in silico promoter analysis for 52 differentiation markers, and exploitation of an EST library from GKs, were filtered according to gene products’ known or putative function and ESTs number in UniGene database, and allowed identification of 298 candidates out of 3,662 genes potentially specific from the last differentiation steps. Half were detected for the first time in epidermis and quantified by quantitative real-time PCR. These genes are linked to various aspects of GKs function, including structural components, lipid metabolism and secretory apparatus, cell signaling, and regulation of transcription. Forty-nine new differentiation-associated genes were identified, and 38 transcription factors in 92 were positively or negatively regulated in the course of differentiation, therefore possibly involved in the final differentiation of GKs. These data give new leads to have a global view of the network involved in epidermal barrier function, and allow in the future a better understanding of several pathologies, including genodermatoses of unknown aetiology. Keywords: Cell type comparison Six independent samples of normal human epidermis were used for this study. For three samples, technical replicates (at the labelling step) were performed (ie AQQ003, AQQ005 and AQQ011 slides are dye-swaps of AQQ002, AQQ004 and AQQ010, respectively). Data from each pair of “swap arrays” were merged and considered as coming from three simple arrays (named AQQ002dw, AQQ004dw and AQQ010dw) for statistical analysis. For each slide, T4 is the test sample (total RNA from granular keratinocytes), and T1 the reference sample (total RNA from basal keratinocytes of the same subject), and both come from the same biological sample.
2010-08-31 | E-GEOD-13263 | biostudies-arrayexpress
Project description:SAGE libraries from cultured, differentiated keratinocytes and human epidermis, both normal and affected by actinic keratosis Keywords = Keratinocyte, Epidermis, Homo sapiens, Actinic Keratosis, TNF alpha
2002-02-21 | E-GEOD-31 | biostudies-arrayexpress
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
Project description:SAGE libraries from cultured, differentiated keratinocytes and human epidermis, both normal and affected by actinic keratosis Keywords = Keratinocyte, Epidermis, Homo sapiens, Actinic Keratosis, TNF alpha
2002-02-22 | GSE31 | GEO
Project description:Transcription profiling of Lgr6+ keratinocyte populations in the epidermis and hair follicle
| PRJEB9207 | ENA
Project description:In epidermis, granular keratinocytes are responsible for the synthesis of a great number of proteins of high tissue-specificity, and required for the epidermal barrier establishment and the regulation of the desquamation process. This project aims at characterizing the physiopathological function of genes implicated in these processes, and in the short term, defining their expression level in the course of keratinocyte differentiation. Pangenomic oligonucleotide microarrays are used to compare their expression between two cell populations enriched in basal or granular keratinocytes (T1 and T4 fractions resp.), obtained by successive incubations in trypsin solution of six independent normal human epidermis samples. Real-time quantitative PCR experiments were further performed to ensure the validity of the profiling for each candidate gene identified from microarrays data, and results of this multitechnique approach will be the object of a forthcoming publication. These results will be the basis for a better understanding of dermatological hyperkeratotic pathologies. Within epidermis, keratinocytes achieve a differentiation program culminating in cornification, a programmed cell death required for the establishment of the barrier function. A complex genetic regulatory network underlies the numerous biochemical modifications taking place in the last living cells, the granular keratinocytes (GKs), but very few transcription factors specific from this process were identified. Here we describe a large-scale, multitechnique approach performed on cells purified from normal human epidermis, and mainly focused on identification of these regulators. We performed microarray experiments to compare gene expression in cell fractions enriched in granular or basal keratinocytes. These data, with in silico promoter analysis for 52 differentiation markers, and exploitation of an EST library from GKs, were filtered according to gene products’ known or putative function and ESTs number in UniGene database, and allowed identification of 298 candidates out of 3,662 genes potentially specific from the last differentiation steps. Half were detected for the first time in epidermis and quantified by quantitative real-time PCR. These genes are linked to various aspects of GKs function, including structural components, lipid metabolism and secretory apparatus, cell signaling, and regulation of transcription. Forty-nine new differentiation-associated genes were identified, and 38 transcription factors in 92 were positively or negatively regulated in the course of differentiation, therefore possibly involved in the final differentiation of GKs. These data give new leads to have a global view of the network involved in epidermal barrier function, and allow in the future a better understanding of several pathologies, including genodermatoses of unknown aetiology. Keywords: Cell type comparison
2010-08-31 | GSE13263 | GEO