Xenopus gene ag1 influence on the skin would healing in mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE315128 | GEO | 2026/03/11
REPOSITORIES: GEO
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Project description:Mammals heal faster with imperfect fibrotic scars, while amphibians regenerate slower with scarless wound healing. These observations support the prevailing paradigm that speed of wound closure is inversely related to repair quality. Here we find evidence that this is a false trade-off. In multiple injury models, mice lacking CXCR2 (CXCR2-KO) globally improved both speed and quality of skin wound healing, including hair regeneration. We found CXCR2 primarily expressed in neutrophils, and injury induced neutrophils to secrete neutrophil extracellular traps (NETs). Mice engineered to be specifically deficient in myeloid CXCR2 or NET production partially recreated the phenotype with improved early speed of wound closure. Thus, CXCR2+ neutrophils regulate the speed of wound closure.
2024-10-03 | GSE245864 | 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 | 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
Project description:Previously, we developed a new model of diabetes-induced wound healing impairment in skin-humanized mice models that faithfully recapitulates the major histo-physiological features of such skin repair-deficient condition. Aiming to dissect the molecular mechanisms responsible for the delayed wound closure, global gene expression studies were performed.
2021-02-01 | GSE147890 | GEO
Project description:Gene expression during embryonic wound healing of Xenopus laevis.
| PRJNA479858 | ENA
Project description:The skin serves as a vital barrier against external damage. Severe wounds, particularly chronic ones, compromise this barrier, which can result in infection, pain, disfigurement and life-threatening complications. However, there are limited pharmacological interventions that can substantially enhance wound healing. Gene therapy offers a promising strategy by enabling the sustained local expression of therapeutic factors. In this study, we demonstrate that the AAV-DJ vector efficiently delivers genes to dermal cells, where transgene expression exhibits a self-limiting profile characterized by robust expression during wound healing, followed by a rapid decline after cell proliferation and wound closure. Furthermore, we show that AAV-mediated delivery of the fibroblast growth factors Fgf1, Fgf2 and Fgf7 (KGF) significantly accelerates wound closure, with Fgf7 having the most pronounced effect. Mechanistically, dermally expressed FGF7 promotes keratinocyte proliferation and migration in a paracrine manner, thereby enhancing re-epithelialization. Furthermore, the downstream factor SFN (Stratifin, 14-3-3σ) was identified as a partial mediator of the pro-healing effects of FGF7. Taken together, these results demonstrate the efficacy and safety of AAV-mediated gene delivery in promoting wound healing and provide a foundation for extending gene therapy applications to other skin disorders.
2025-09-16 | GSE307763 | GEO
Project description:Xenopus laevis juvenile frogs are uniquely capable of scarless skin regeneration, but the cellular and molecular mechanisms guiding this process remain incompletely understood. Macrophages are known as key regulators of wound healing, yet how their phenotypes shift over time and influence downstream regeneration in X. laevis has not been previously defined. It is well established that macrophage functions are imperative to mammalian wound healing. In vertebrate biology, macrophage polarization is dictated by two colony-stimulating factor-1 (CSF1) receptor ligands: CSF1 and interleukin-34 (IL34). While IL34 in mammals is critical to the development of epidermal macrophages known as Langerhans cells, the contribution of CSF1- and IL34-derived macrophages to skin wound repair remains unexplored. Pertinently, using the X. laevis model, previous work from our lab showed that CSF1- and IL34- macrophages are functionally distinct, formulating our hypothesis that these subsets play distinct roles during different phases of cutaneous wound repair. We therefore characterized full-thickness (epidermis and dermis) skin wounds in juvenile X. laevis during regeneration, analyzing transcript levels reflecting: M( infiltration (csf1r) and phenotype abundance (csf1 and il34), fibroblast activation (αSMA/acta2), and wound bed collagen composition (Picrosirius red staining). To assess the functional roles of macrophage phenotypes, we enriched wounds with recombinant X. laevis CSF1, IL34, or a vector control 3 days post-wounding (dpw) and analyzed wound responses at 7 and 14 dpw. Normal scarless regeneration in these juveniles demonstrated that macrophages transiently accumulated in the wound bed, peaking at 7–14 dpw. This coincided with elevated csf1 expression, which later declined as il34 levels rose. Fibroblast activation into myofibroblasts as well as collagen deposition followed this cytokine shift and restored collagen to pre-wound levels by 60 dpw. Subcutaneous IL34 enrichment at 3 dpw led to significantly increased αSMA expression at 7 and 14 dpw, a higher type I:III collagen ratio at 7 dpw, and suppression of inflammatory mediators coupled with enhancement of other, anti-inflammatory mediators at 7dpw. CSF1 enrichment had no significant effect on αSMA expression or subsequent collagen deposition, but did show a bias towards inflammatory mediators and the suppression of resolving and pro-reparative transcripts at 7 dpw. These findings suggest that early IL34 supplementation promotes a pro-regenerative macrophage phenotype that enhances myofibroblast activation and matrix remodeling while early CSF1 supplementation may contribute to prolonged inflammation and impaired tissue regeneration. Temporal modulation of macrophage-derived signals, particularly IL34, plays a critical role in directing scarless skin regeneration in X. laevis. These findings identify a conserved immunoregulatory axis with potential relevance to improving wound healing in non-regenerative species. Xenopus laevis juvenile frogs are uniquely capable of scarless skin regeneration, but the cellular and molecular mechanisms guiding this process remain incompletely understood. Macrophages are known as key regulators of wound healing, yet how their phenotypes shift over time and influence downstream regeneration in X. laevis has not been previously defined. It is well established that M( functions are imperative to mammalian wound healing. In vertebrate biology, M( polarization is dictated by two colony-stimulating factor-1 (CSF1) receptor ligands: CSF1 and interleukin-34 (IL34). While IL34 in mammals is critical to the development of epidermal M(s known as Langerhans cells, the contribution of CSF1- and IL34-derived macrophages to skin wound repair remains unexplored. Pertinently, using the X. laevis model, previous work from our lab showed that CSF1- and IL34- M(s are functionally distinct, formulating our hypothesis that these subsets play distinct roles during different phases of cutaneous wound repair. We therefore characterized full-thickness (epidermis and dermis) skin wounds in juvenile X. laevis during regeneration, analyzing transcript levels reflecting: macrophage infiltration (csf1r) and phenotype abundance (csf1 and il34), fibroblast activation (αSMA/acta2), and wound bed collagen composition (Picrosirius red staining). To assess the functional roles of macrophage phenotypes, we enriched wounds with recombinant X. laevis CSF1, IL34, or a vector control 3 days post-wounding (dpw) and analyzed wound responses at 7 and 14 dpw. Normal scarless regeneration in these juveniles demonstrated that macrophages transiently accumulated in the wound bed, peaking at 7–14 dpw. This coincided with elevated csf1 expression, which later declined as il34 levels rose. Fibroblast activation into myofibroblasts as well as collagen deposition followed this cytokine shift and restored collagen to pre-wound levels by 60 dpw. Subcutaneous IL34 enrichment at 3 dpw led to significantly increased αSMA expression at 7 and 14 dpw, a higher type I:III collagen ratio at 7 dpw, and suppression of inflammatory mediators coupled with enhancement of other, anti-inflammatory mediators at 7dpw. CSF1 enrichment had no significant effect on αSMA expression or subsequent collagen deposition, but did show a bias towards inflammatory mediators and the suppression of resolving and pro-reparative transcripts at 7 dpw. These findings suggest that early IL34 supplementation promotes a pro-regenerative M( phenotype that enhances myofibroblast activation and matrix remodeling while early CSF1 supplementation may contribute to prolonged inflammation and impaired tissue regeneration. Temporal modulation of macrophage-derived signals, particularly IL34, plays a critical role in directing scarless skin regeneration in X. laevis. These findings identify a conserved immunoregulatory axis with potential relevance to improving wound healing in non-regenerative species.
2025-10-22 | GSE306422 | GEO
Project description:Wound healing is facilitated by neoangiogenesis, a complex process that is essential to tissue repair in response to injury. MicroRNAs are small, non-coding RNAs that can regulate the wound healing process including stimulation of impaired angiogenesis that is associated with Type-2 diabetes (T2D). Expression of miR-409-3p was significantly increased in the non-healing skin wounds of patients with T2D compared to the non-wounded normal skin, and in the skin of a murine model with T2D. In response to high glucose, neutralization of miR-409-3p markedly improved EC growth and migration in human umbilical vein endothelial cells (HUVECs), promoted wound closure and angiogenesis as measured by increased CD31 in human skin organoids, while overexpression attenuated EC angiogenic responses. Bulk mRNA-Seq transcriptomic profiling revealed BTG2 as a target of miR-409-3p, where overexpression of miR-409-3p significantly decreased BTG2 mRNA and protein expression. A 3′ untranslated region (3′-UTR) luciferase assay of BTG2 revealed decreased luciferase activity with overexpression of miR-409-3p, while inhibition had opposite effects. Mechanistically, in response to high glucose, miR-409-3p deficiency in ECs resulted in increased mTOR phosphorylation meanwhile BTG2 silencing significantly decreased mTOR phosphorylation. Endothelial specific and tamoxifen-inducible miR-409-3p knock out mice (MiR-409IndECKO) with hyperglycemia that underwent dorsal skin wounding showed significant improvement of wound closure, increased blood flow, granulation tissue thickness (GTT), and CD31 that correlated with increased BTG2 expression. Taken together, our results show that miR-409-3p is a critical mediator of impaired angiogenesis in diabetic skin wound healing.
2025-01-31 | GSE252852 | GEO
Project description:Effective therapy of wounds is difficult, especially for chronic, non-healing wounds, and novel therapeutics are urgently needed. This challenge can be addressed with bioactive wound dressings providing a microenvironment and facilitating cell proliferation and migration, ideally incorporating actives which initiate and/or progress effective healing upon release. In this context, electrospun scaffolds loaded with growth factors emerged as promising wound dressings due to their biocompatibility, similarity to the extracellular matrix and potential for controlled drug release. In this study, electrospun core-shell fibers were designed composed of a combination of polycaprolactone and polyethylene oxide. Insulin, a proteohormon with growth factor characteristics, was successfully incorporated into the core and was released in a controlled manner. The fibers exhibited favorable mechanical properties and a surface guiding cell migration for wound closure in combination with a high uptake capacity for wound exudate. Biocompatibility and significant wound healing effects were shown in interaction studies with human skin cells. As a new approach, analysis of the wound proteome in treated ex vivo human skin wounds clearly demonstrated a remarkable increase in wound healing biomarkers. Based on these findings, insulin-loaded electrospun wound dressings bear a high potential as effective wound healing therapeutics overcoming current challenges in the clinics.
2022-12-19 | PXD034076 | Pride
Project description:Scarring is a common outcome of wound healing in adult skin, often leading to fibrotic tissue that lacks the functional and aesthetic properties of normal, uninjured skin. To effectively reduce and prevent scar formation, understanding the cellular players involved in fibrosis is crucial. Among these, macrophages and mesenchymal cells have received significant attention due to their vital roles in both tissue regeneration and fibrosis. Research has shown that depleting macrophages during the early stages of wound healing reduces the number of myofibroblasts in the wound bed and delays wound closure, but results in reduced scar formation, suggesting that macrophages contribute to fibrosis by regulating mesenchymal cells. However, there remains a need for unbiased, high-throughput approaches to precisely investigate the mechanisms through which macrophages regulate and induce mesenchymal subtypes in scar formation. In this study, we performed single-cell RNA sequencing to investigate changes in mesenchymal cell subpopulations during adult skin wound healing in a conditional macrophage depletion mouse model, macrophage Fas-induced apoptosis (MaFIA).
2025-12-22 | GSE280334 | GEO