CXCR2 knockout promotes skin and hair regeneration without scarring
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE245864 | GEO | 2024/10/03
REPOSITORIES: GEO
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Project description:Foetal skin is known to heal without scar. This ability is lost in the third trimester of gestation. In mouse, scarless wound healing was reported until the day 15-16 of gestation. A range of factors that could explain the mechanisms of scarless skin wound healing have been identified, to mention reduced immune response, a greater proportion of collagen type III, hyaluronic acid and transforming growth factor beta isoform 3. The involvement of epigenetic changes, which are known to determine developmental processes, has not been examined in the context of scarless foetal skin healing so far. We performed the microarray analysis methylome and transcriptome of murine foetal dorsal skin at embryonic day 15 contrasted with those in later phases at embryonic days 18-19 as well as the in the adult mouse. The group of genes which show decreased methylation status in the foetal skin before the loss of ability to scarless healing between embryonic day 15 and 18 are enriched with transcriptional factors involved in embryonic morphogenesis, epithelium development, neuron differentiation, and synapse functions. The genes with increased methylation after the transition are associated with cell death and epithelial cell differentiation, inflammatory and wounding response and the degradation of hyaluronic acid. A substantial part of DNA methylation differences observed between embryonic day 15 and 18 were retained later at embryonic day 19 and in adults and remarkably correlated with gene expression changes. A major part of genes encoding the key factors responsible for cutaneous wound healing show significant changes in gene expression following the transition from scar free to normal healing. The results show that skin methylome and transcriptome undergoe extensive alterations following the loss of ability to scarless healing, while the functions associated with the changes imply their central role in skin wound repair.
2016-12-31 | GSE67877 | GEO
Project description:Foetal skin is known to heal without scar. This ability is lost in the third trimester of gestation. In mouse, scarless wound healing was reported until the day 15-16 of gestation. A range of factors that could explain the mechanisms of scarless skin wound healing have been identified, to mention reduced immune response, a greater proportion of collagen type III, hyaluronic acid and transforming growth factor beta isoform 3. The involvement of epigenetic changes, which are known to determine developmental processes, has not been examined in the context of scarless foetal skin healing so far. We performed the microarray analysis methylome and transcriptome of murine foetal dorsal skin at embryonic day 15 contrasted with those in later phases at embryonic days 18-19 as well as the in the adult mouse. The group of genes which show decreased methylation status in the foetal skin before the loss of ability to scarless healing between embryonic day 15 and 18 are enriched with transcriptional factors involved in embryonic morphogenesis, epithelium development, neuron differentiation, and synapse functions. The genes with increased methylation after the transition are associated with cell death and epithelial cell differentiation, inflammatory and wounding response and the degradation of hyaluronic acid. A substantial part of DNA methylation differences observed between embryonic day 15 and 18 were retained later at embryonic day 19 and in adults and remarkably correlated with gene expression changes. A major part of genes encoding the key factors responsible for cutaneous wound healing show significant changes in gene expression following the transition from scar free to normal healing. The results show that skin methylome and transcriptome undergoe extensive alterations following the loss of ability to scarless healing, while the functions associated with the changes imply their central role in skin wound repair.
2016-12-31 | GSE67876 | GEO
Project description:The MRL/MpJ mouse strain is known as a model of mammalian regeneration. The strain exhibits an unusual capacity in regenerative wound healing manifested by scarless ear-hole closure and enhanced regeneration response reported in other organs. A significant feature of the strain is that the adult MRL/MpJ mouse retains several embryonic biochemical characteristics, including increased expression of stem cell markers. As the regenerative response after injury is rather limited in mammals the MRL/MpJ mouse is a great model to study the molecular and cellular basis of scarless wound healing. We report here the analysis of genome-wide transcriptomic profiles in the heart, ear, spleen, liver and bone marrow of the MRL/MpJ mouse. We used gene expression microarray, which interrogates 44.170 of mouse transcripts, in order to identify the genes exhibiting remarkable differences in expression in the MRL/MpJ mouse compared to two reference strains: C57BL/6J and BALB/c. The comparison revealed hundreds of differentially expressed transcripts. Significant enrichments of genes engaged in retinol metabolism, peroxisome proliferator-activated receptor (PPAR), wound healing, and homeobox pathways distinguishes the differentially expressed transcripts up-regulated in the MRL/MpJ mouse, whereas the genes related to immune response, including including response to wounding are greatly enriched among those down-regulated. The same functional categories were associated with remarkable parallels between the transcriptomic patterns in murine neonates and the adult MRL/MpJ mouse.
2015-12-30 | GSE64624 | GEO
Project description:Scarring is a normal outcome of the wound healing program, but excessive secretion of ECM proteins such as collagen can lead to fibrosis and compromise tissue function. Despite the widespread occurrence of fibrosis, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts. We designed membrane permeant-peptide inhibitors that specifically target and disrupt the primary interface between TANGO1 and cTAGE5, an interaction that is required for collagen export from endoplasmic reticulum exit sites (ERES). Dissociation of the TANGO1 and cTAGE5 complex leads to their partial degradation and a consequent inhibition in the secretion of several ECM components, including collagens. Peptide inhibitor treatment in zebrafish resulted in altered tissue architecture and reduced granulation tissue formation during cutaneous wound healing. The inhibitors reduced secretion of several ECM proteins, including collagens, fibrillin and fibronectin in human dermal fibroblasts and in cells obtained from patients with a generalized fibrotic disease (scleroderma). Taken together, this targeted interference in the TANGO1-cTAGE5 binding interface enables therapeutic modulation of ERES function in ECM hypersecretion, during wound healing and fibrotic processes.
2024-04-28 | PXD041678 | Pride
Project description:The cornea, transparent and outermost structure of camera-type eyes, is prone to environmental challenges, but has remarkable wound healing capabilities which enables to preserve vision. The manner in which cell plasticity impacts wound healing remains to be determined. In this study, we report rapid wound closure after zebrafish corneal epithelium abrasion. Furthermore, by investigating the cellular and molecular events taking place during corneal epithelial closure, we show the induction of a bilateral response to a unilateral wound. Our transcriptomic results, together with our TGF-beta receptor inhibition experiments, demonstrate conclusively the crucial role of TGF-beta signaling in corneal wound healing. Finally, our results on Pax6 expression and bilateral wound healing, demonstrate the decisive impact of epithelial cell plasticity on the pace of healing. Altogether, our study describes terminally differentiated cell competencies in the healing of an injured cornea. These findings will enhance the translation of research on cell plasticity to organ regeneration.
2022-01-20 | GSE193784 | GEO
Project description:This is an ordinary differential equation-based mathematical model describing the inflammatory phase of the wound healing response. The model describes the interactions in the wound between wound debris, pathogens, neutrophils and macrophages, as well as the modulation of these interactions by estrogen and cortisol.
2024-09-02 | BIOMD0000000855 | BioModels
Project description:The methylome of murine foetal skin and scarless wound healing
| PRJNA281103 | ENA
Project description:The transcriptome of murine foetal skin and scarless wound healing
| PRJNA281102 | ENA
Project description:Skin wound healing is one of the major prevalent medical problems in the worldwide. Wound healing involves multi-process synergy and re-epithelialization is an essential part of wound healing. Histone H3K36 tri-methylase Setd2 has been extensively studied in different biological processes and diseases. However, the function of Setd2 in the wound healing remains unclear. To elucidate the biological role of Setd2 in the skin wound healing, conditional gene targeting was employed to establish epidermis-specific Setd2-deficient mice. We found that Setd2 deficiency resulted in accelerated re-epithelialization during cutaneous wound healing by promoting keratinocytes proliferation and migration. Furthermore, we demonstrated that loss of Setd2 activated the AKT/mTOR pathway, and pharmacological inhibitions of AKT and mTOR with MK2206 and rapamycin delayed wound closure, respectively. In conclusion, our results reveal the essential role of Setd2 in skin wound healing that is Setd2 loss promotes cutaneous wound healing via activation of AKT/mTOR signaling.
2020-12-25 | GSE163860 | GEO
Project description:Skin wound healing is one of the major prevalent medical problems in the worldwide. Wound healing involves multi-process synergy and re-epithelialization is an essential part of wound healing. Histone H3K36 tri-methylase Setd2 has been extensively studied in different biological processes and diseases. However, the function of Setd2 in the wound healing remains unclear. To elucidate the biological role of Setd2 in the skin wound healing, conditional gene targeting was employed to establish epidermis-specific Setd2-deficient mice. We found that Setd2 deficiency resulted in accelerated re-epithelialization during cutaneous wound healing by promoting keratinocytes proliferation and migration. Furthermore, we demonstrated that loss of Setd2 activated the AKT/mTOR pathway, and pharmacological inhibitions of AKT and mTOR with MK2206 and rapamycin delayed wound closure, respectively. In conclusion, our results reveal the essential role of Setd2 in skin wound healing that is Setd2 loss promotes cutaneous wound healing via activation of AKT/mTOR signaling.
2020-12-25 | GSE163858 | GEO