SOX2 epidermal overexpression promotes cutaneous wound healing via activation of EGFR/MEK/ERK signaling mediated by EGFR ligands
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE118859 | GEO | 2019/09/02
REPOSITORIES: GEO
Similar Datasets
Project description:SOX2 epidermal overexpression promotes cutaneous wound healing via activation of EGFR/MEK/ERK signaling mediated by EGFR ligands
| PRJNA487061 | ENA
Project description:Oral mucosa contains a unique transcriptional network that primes oral wounds for rapid resolution in humans. Our previous work identified genes that were consistently upregulated in the oral mucosa and demonstrated that induction of one of the identified genes, transcription factor SOX2, promoted cutaneous wound healing in mice. In this study, we investigated the molecular and cellular mechanisms by which SOX2 accelerates wound healing in skin. RNA-sequencing analysis showed that SOX2 induced a proliferative and wound-activated phenotype in skin keratinocytes prior to wounding. During wound healing, SOX2 induced proliferation of epithelial and connective tissue cells and promoted angiogenesis. Chromatin immunoprecipitation assay revealed that SOX2 directly regulates expression of EGFR ligands, resulting in activation of EGFR. In vitro, skin keratinocytes overexpressing SOX2 promoted cell migration via the EGFR/MEK/ERK pathway. We conclude that induction of SOX2 in skin keratinocytes accelerates cutaneous wound healing by promoting keratinocyte migration and proliferation, and enhancement of angiogenesis via upregulation of EGFR ligands and activation of EGFR/MEK/ERK pathway. Through the identification of putative cutaneous SOX2 targets, such as HBEGF, this study opens venues to determine clinical targets for treatment of skin wounds.
| S-EPMC6650375 | biostudies-literature
Project description:We show that a combinatorial upregulation of SOX2 and hyperglycemia in cutaneous keratinocytes triggers a pro-healing signature and increased neutrophil chemoattraction, putatively by Ccr2, Ccr5, and Csf3r signaling. Neutrophil depletion and deregulation through the TREM1/FOXM1 pathway are directly implicated in diabetic foot ulcer (DFU) pathophysiology. Our results highlight the role of neutrophil recruitment in wound healing and can be used to explore potential therapeutic targets for DFUs in patients.
2024-07-22 | GSE266638 | GEO
Project description:Defective fibroblast migration cause delayed wound healing (WH) and chronic skin lesions. Autologous micrograft (AMG) therapies have recently emerged as a new effective treatment able to improve wound healing capacity. However, the molecular mechanisms connecting their beneficial outcomes with the wound healing process are still unrevealed. Here, we show that AMG modulates primary fibroblast migration and accelerates skin re-epithelialization without affecting cell proliferation. We demonstrate that AMG is enriched in a pool of WH-associated growth factors that may provide the initiation signal for faster endogenous wound healing response. This, in turn leads to increased cell migration rate by elevating activity of ERK and subsequent activation of matrix metalloproteinase expression and their extracellular enzymatic activity. Moreover, AMG-treated wounds showed increased granulation tissue formation and organized collagen content. Overall, we shed light on AMG molecular mechanism supporting its potential to trigger highly improved wound healing process.
2020-01-01 | GSE123829 | GEO
Project description:Impaired skin wound healing is a significant global health issue, especially among the elderly. Wound healing is a well-orchestrated process involving the sequential phases of inflammation, proliferation, and tissue remodeling. Although wound healing is a highly dynamic and energy-requiring process, the role of metabolism remains largely unexplored. By combining transcriptomics and metabolomics of human skin biopsy samples, we mapped the core bioenergetic and metabolic changes in normal acute as well as chronic wounds in elderly subjects. We found upregulation of glycolysis, the tricarboxylic acid cycle, glutaminolysis, and β-oxidation in the later stages of acute wound healing and in chronic wounds. To ascertain the role of these metabolic pathways on wound healing, we targeted each pathway in a wound healing assay as well as in a human skin explant model using metabolic inhibitors and stimulants. Enhancement or inhibition of glycolysis and, to a lesser extent, glutaminolysis had a far greater impact on wound healing than similar manipulations of oxidative phosphorylation and fatty acid β-oxidation. These findings increase the understanding of wound metabolism and identify glycolysis and glutaminolysis as potential targets for therapeutic intervention.
2024-07-02 | MTBLS3315 | MetaboLights
Project description:We performed RNA-seq on primary human keratinocytes treated with mevastatin to identify the molecular mechanisms by which statins promote wound healing. Our results identified a mevastatin gene signature that activated and modulated the EGF signaling to trigger an anti-proliferative and pro-migratory phenotype. In addition, EGFR signaling is downregulated in chronic non-healing wounds and mevastatin was able to restore EGFR signaling by downregulating caveolin proteins, a known inhibitor of EGFR signaling and wound healing. These results demonstrate that statins may have considerable therapeutic potential for patients with chronic wounds that can be rapidly translated to clinical use.
2024-06-30 | GSE137441 | GEO
Project description:Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the main events participating in the healing of a wound, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process, but allow exploring many unanswered features of the healing response; e.g., which are the signal(s) responsible for initiating tissue remodeling? How is the sealing of the epithelia achieved? Or which are the inhibitory cues that cancel the healing machinery upon completion? Answering these and other questions demands in first place the identification and functional analysis of wound-specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method to culture imaginal discs that allows live imaging and biochemical analysis and is healing-permissive. Employing this approach, we performed a comparative genome-wide profiling between those Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. This lets us identify a set of potential wound-specific genes. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in a healing assay. This non-saturated analysis defines a relevant set of new genes whose changes in expression levels are functionally significant for proper tissue repair. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound response. We developed a healing-permissive in vitro culture system for fly imaginal discs: we used one-channel microarrays for comparing healing-engaged cells (showing activation of the JNK signaling cascade) to cells not participating in healing (silent JNK activity) in wounded wing imaginal discs in culture. Employing this method, we aimed detecting the relevant genes involved in disc healing through microarray analysis. We compared cells actively involved in healing to those not involved and identified a whole set of upregulated or downregulated genes. They were annotated, clustered by expression profiles, chromosomal locations and presumptive functions. Most importantly, we functionally tested them genetically in a healing assay.
2015-04-13 | E-GEOD-62863 | biostudies-arrayexpress
Project description:This study is the first to report on the transcriptome of healing gingiva and to provide an integrative analysis of mRNA/miRNA expression during human oral wound healing; the results offer novel insights into the participating molecular mechanisms and suggest that miR-124-3p and PXDN could be potential wound healing therapeutic targets.
2021-03-06 | GSE111523 | GEO
Project description:This study is the first to report on the miRNome of healing gingiva and to provide an integrative analysis of mRNA/miRNA expression during human oral wound healing; the results offer novel insights into the participating molecular mechanisms and suggest that miR-124-3p and PXDN could be potential wound healing therapeutic targets.
2021-03-06 | GSE111466 | GEO