Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA218008 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Epidermal keratinocytes respond to extracellular influences by activating cytoplasmic signal transduction pathways that change the transcriptional profiles of affected cells. To define responses to two such pathways, p38 and ERK, we used SB203580 and PD98059 as specific inhibitors, and identified the regulated genes after 1, 4, 24 and 48 hrs, using Affymetrix’ Hu133Av2 microarrays. Additionally, we compared genes specifically regulated by p38 and ERKs with those regulated by JNK and by all three pathways simultaneously. We find that the p38 pathway induces the expression of extracellular matrix and proliferation-associated genes, while suppressing microtubule-associated genes; the ERK pathway induces the expression of nuclear envelope and mRNA splicing proteins, while suppressing steroid synthesis and mitochondrial energy production enzymes. Both pathways promote epidermal differentiation and induce feedback inactivation of MAPK signaling. c-FOS, SRY and N-Myc appear to be the principal targets of the p38 pathway, Elk-1 SAP1 and HLH2 of ERK, while FREAC-4, ARNT and USF are common to both. The results for the first time comprehensively define the genes regulated by the p38 and ERK pathways in epidermal keratinocytes and suggest a list of targets potentially useful in therapeutic interventions. Human epidermal keratinocytes are grown in Keratinocyte Serum-Free Medium (Gibco) supplemented with 0.05 mg/ml bovine pituitary extract, 2.5 ng/ml epidermal growth factor, 0.09 mM CalCl2 and 1% penicillin/streptomycin (KGM). They are switched to Keratinocyte Serum Free-Media (Gibco) supplemented only with 1% penicillin/streptomycin (KBM) 24 h prior to commencing experiments. A set is left as controls, others treated with 5 uM JNK inhibitor SP600125, 15 uM p38 inhibitor SB203580, or 50 um ERK inhibitor PD98059. Timecourse of treated and parellel control samples over a 48 hr period was performed.
2013-09-05 | E-GEOD-50591 | biostudies-arrayexpress
Project description:Epidermal keratinocytes respond to extracellular influences by activating cytoplasmic signal transduction pathways that change the transcriptional profiles of affected cells. To define responses to two such pathways, p38 and ERK, we used SB203580 and PD98059 as specific inhibitors, and identified the regulated genes after 1, 4, 24 and 48 hrs, using Affymetrix’ Hu133Av2 microarrays. Additionally, we compared genes specifically regulated by p38 and ERKs with those regulated by JNK and by all three pathways simultaneously. We find that the p38 pathway induces the expression of extracellular matrix and proliferation-associated genes, while suppressing microtubule-associated genes; the ERK pathway induces the expression of nuclear envelope and mRNA splicing proteins, while suppressing steroid synthesis and mitochondrial energy production enzymes. Both pathways promote epidermal differentiation and induce feedback inactivation of MAPK signaling. c-FOS, SRY and N-Myc appear to be the principal targets of the p38 pathway, Elk-1 SAP1 and HLH2 of ERK, while FREAC-4, ARNT and USF are common to both. The results for the first time comprehensively define the genes regulated by the p38 and ERK pathways in epidermal keratinocytes and suggest a list of targets potentially useful in therapeutic interventions.
2013-09-05 | GSE50591 | GEO
Project description:Transcription profiling of mouse primary hair placode keratinocytes compared to interfollicular epidermal keratinocytes
2016-03-07 | E-MTAB-4535 | ExpressionAtlas
Project description:Covering denuded dermal surface after injury requires migration, proliferation and differentiation of skin keratinocytes. To clarify the major traits controlling these intermingled biological events, we surveyed the genomic modifications occurring during the course of a scratch closure of cultured human keratinocytes. Using a DNA microarray approach, we report the identification of 161 new markers of epidermal repair. Expression data, combined with functional analysis performed with specific inhibitors of ERK, p38[MAPK] and PI3 kinases, demonstrate that kinase pathways exert very selective functions by precisely controlling the expression of specific genes. Inhibition of the ERK pathway totally blocks the wound closure and inactivates many early transcription factors and EGF-type growth factors. P38[MAPK] inhibition only delays “healing”, probably in line with the control of genes involved in the propagation of injury-initiated signalling. In contrast, PI3 kinase inhibition accelerates the scratch closure and potentiates the scratch-dependent stimulation of three genes related to epithelial cell transformation, namely HAS3, HBEGF and Ets1. Our results define in vitro human keratinocyte wound closure as a reparation process resulting from a fine balance between positive signals controlled by ERK and p38[MAPK], and negative ones triggered off by PI3 kinase. The perturbation of any of these pathways might lead to dysfunction in the healing process, as those observed in pathological wounding phenotypes, such as hypertrophic scars or keloids. Keywords: Transcriptome of healing keratinocytes
2007-12-30 | GSE6820 | GEO
Project description:Transcription profiling by array of human epidermal keratinocytes after treatment with interleukin 20 subfamily cytokines
2025-01-24 | E-GEOD-7216 | ExpressionAtlas
Project description:Bis-2-chloroethyl sulfide (sulfur mustard, SM) is a potent alkylating agent and vesicant. Exposure to SM results in activation of numerous signaling cascades, including mitogen-activated protein kinase (MAPK) signaling pathways. These pathways include the Erk, p38, and JNK pathways, which are involved in cell growth, inflammation, and stress signaling. However, the precise roles of these pathways in SM toxicity have not been fully elucidated. We used Western blotting and microarray analysis to examine the activation and role of each pathway following SM exposure in primary human epidermal keratinocytes. Western blotting revealed increased phosphorylation of p38 and JNK following SM exposure; however, phosphorylation of Erk was equivocal, suggesting that growth conditions may impact activation of Erk by SM. We used pharmacologic inhibitors to target each MAPK and then compared the gene expression profiles to identify SM-induced gene networks regulated by each MAPK. Cells were pretreated with 10 µM SB 203580 (p38 inhibitor), PD 98059 (Erk inhibitor), or SP 600125 (JNK inhibitor) 60 minutes before exposure to 200 µM SM. Cells were harvested at 1h, 4h, and 8h post-exposure, and RNA was extracted for synthesis of microarray probes. Probes were hybridized to Affymetrix U133 Plus 2.0 arrays for gene expression profiling. Analysis of variance was performed to identify genes significantly modulated due to pharmacologic inhibition in SM-exposed cells. Pathway mapping confirmed alterations in SM-induced Erk, JNK, and p38 MAPK signaling due to pharmacologic inhibition. SM-induced expression of IL-8, IL-6, and TNF-alpha was decreased by p38 MAPK inhibition, but not by inhibition of other MAPKs. Based on the number of significant pathways mapped to each MAPK in the presence and absence of inhibitors, the p38 MAPK pathway appeared to be the MAPK pathway most responsive to SM exposure. Interestingly, pathway mapping of the microarray data identified potential cross-talk between MAPK signaling pathways and other pathways involved in SM-induced signaling. Mining of these results will increase our understanding of the role of MAPK pathways in SM-induced signal transduction and may identify potential therapeutic targets for medical countermeasure development.
2018-06-15 | GSE29587 | GEO
Project description:Transcriptional signature of wounded keratinocytes reveals selective roles for ERK1/2, P38 and PI3K signalling pathways
| PRJNA99175 | ENA
Project description:Studies were undertaken to determine whether oscillatory behavior in the extracellular signal regulated kinase (ERK) pathway results in unique gene regulation patterns. Microarray analysis was performed on three subcloned populations of human keratinocytes with distinct ERK signaling/oscillation phenotypes. Microarray analysis identified 45 genes that overlapped between 2 subclones with oscillation phenotypes but not in the subclone which is non-oscillatory. Transcription factor networks revealed a role for MED1 in mediating ERK oscillation-dependent gene expression, which was confirmed with Western blot analysis. Further experimentation confirmed a role for p38 in the mediation of MED1 phosphorylation and ERK oscillatory behavior. hTERT-immortalized normal human keratinocytes (provided by Dr. Jerry Shay, The University of Texas Southwestern Medical Center) were stably transfected with ERK1-green fluorescent protein chimera and stable subclones were isolated with distinct ERK activation/oscillation patterns: Clone #1 exhibits transient ERK activation with ligand activation but does not oscillate; Clone #2 exhibits persistent ERK oscillations that are dependent on ligand activation; and Clone #3 exhibits spontaneous ERK oscillations in the absence of ligand activation.
2014-03-13 | E-GEOD-55823 | biostudies-arrayexpress
Project description:Transcriptional profile of human epidermal keratinocytes in response to formaldehyde
| PRJNA307346 | ENA
Project description:Adhesion of basal keratinocytes to the underlying extracellular matrix (ECM) plays a key role in the control of skin homeostasis and response to injury. Integrin receptors indirectly link the ECM to the cell cytoskeleton through large protein complexes called focal adhesions (FA). FA also function as intracellular biochemical signaling platforms to enable cells to respond to changing extracellular cues. The α4β1 and α9β1 integrins are both expressed in basal keratinocytes, share some common ECM ligands, and have been shown to promote wound healing in vitro and in vivo. However, their roles in maintaining epidermal homeostasis and relative contributions to pathological processes in the skin remain unclear. We found that α4β1 and α9β1 occupied distinct regions in monolayers of a basal keratinocyte cell line (NEB-1). During collective cell migration (CCM), α4 and α9 integrins co-localized along the leading edge. Pharmacological inhibition of α4β1 and α9β1 integrins increased keratinocyte proliferation and induced a dramatic change in cytoskeletal remodeling and FA rearrangement, detrimentally affecting collective cell migration (CCM). Further analysis revealed that α4β1/α9β1 integrins suppress ERK1/2 activity to control migration through the regulation of downstream kinases including Mitogen and Stress Activated Kinase 1 (MSK1). We performed LC-MS/MS analysis of α4β1/α9β1 adhesion complexes to identify partners that could regulate ERK activity.
2022-02-17 | PXD027944 | Pride