Self-Limiting AAV-Mediated FGF7 Expression Promoters Re-epithelialization and Accelerates Cutaneous Wound Healing
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1327295 | ENA |
REPOSITORIES: ENA
Similar Datasets
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:BackgroundAutologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair.MethodsFull-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo.ResultsPRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14.ConclusionPRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.
| S-EPMC7427034 | biostudies-literature
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:BackgroundMatricellular proteins, including periostin, are important for tissue regeneration.Methods and findingsPresently we investigated the function of periostin in cutaneous wound healing by using periostin-deficient ⁻/⁻ mice. Periostin mRNA was expressed in both the epidermis and hair follicles, and periostin protein was located at the basement membrane in the hair follicles together with fibronectin and laminin γ2. Periostin was associated with laminin γ2, and this association enhanced the proteolytic cleavage of the laminin γ2 long form to produce its short form. To address the role of periostin in wound healing, we employed a wound healing model using WT and periostin⁻/⁻ mice and the scratch wound assay in vitro. We found that the wound closure was delayed in the periostin⁻/⁻ mice coupled with a delay in re-epithelialization and with reduced proliferation of keratinocytes. Furthermore, keratinocyte proliferation was enhanced in periostin-overexpressing HaCaT cells along with up-regulation of phosphorylated NF-κB.ConclusionThese results indicate that periostin was essential for keratinocyte proliferation for re-epithelialization during cutaneous wound healing.
| S-EPMC3072397 | biostudies-literature
Project description:Impaired re-epithelialization is a hallmark of non-healing, chronic skin wounds. These represent major causes of patient morbidity, particularly amongst ever-increasing ageing and diabetic populations, posing significant challenges to healthcare providers worldwide. Despite many treatment options being available, these often offer limited benefits to healing outcomes. We address the need for more efficacious treatments through evaluation of novel epoxy-tigliane compounds as chronic wound pharmaceuticals, based on their effectiveness in promoting keratinocyte healing responses and re-epithelialization in vivo. Here, we identify that prototype epoxy-tigliane (EBC-46) and analogue (EBC-211), accelerate G1/S and S/G2 cell cycle transitions and proliferation in a normal human keratinocyte cell line of skin origin (HaCaTs). EBC-46 and EBC-211 further induce HaCaT migration/wound repopulation, even with mitomycin C treatment, suggesting epoxy-tiglianes can promote migration/repopulation independently of proliferation. Epoxy-tiglianes modulate keratin, DNA synthesis/replication, cell cycle/proliferation, motility/migration, differentiation, proteinase; and cytokine/chemokine gene expression, to facilitate enhanced responses. Although epoxy-tiglianes down-regulate cytokine/chemokine agonists of keratinocyte proliferation/migration, we demonstrate that enhanced HaCaT responses are mediated through protein kinase C (PKC) phosphorylation and abrogated by inhibition of PKC activation with bisindolylmaleimide-1 (BIM-1). By identifying how epoxy-tiglianes stimulate keratinocyte healing responses, we highlight their potential as novel therapeutics for impaired re-epithelialization associated with non-healing, chronic wounds.
2019-08-01 | GSE122297 | GEO
Project description:BackgroundThe incidence of diabetes-related wounds is widespread, and the treatment is challenging. We found that Moist Exposed Burn Ointment (MEBO) promotes the healing of diabetes-related wounds, but the mechanism is not clear.MethodsThis study aimed to explore the mechanism of MEBO on diabetic wound healing, which may be related to the promotion of re-epithelialization. A full-thickness skin resection model was established in streptozotocin (STZ)-induced diabetic mice. MEBO and Kangfuxin (KFX) were applied to the wound area, and the wound healing rate was analyzed by photographing. The granulation tissue and epidermal thickness, the collagen remodeling rate, and the expression of cytokeratin 10 (CK10), cytokeratin 14 (CK14), Ki67, Collagen I, and Collagen III in the regenerated skin were detected by H&E staining, Masson staining, and immunofluorescence staining, respectively. MEBO and KFX were applied to human immortalized keratinocytes (HaCaT), mouse dermal fibrolasts (MDF) cells, and cell viability, cell migration, and differentiation were determined by CCK-8, scratching assay, RT-qPCR, and Western blot (WB), respectively.ResultsWe found that MEBO significantly promoted the formation of wound granulation tissue and collagen remodeling in diabetic mice. The application of MEBO to diabetic wounds not only promoted the formation of hair follicles and sebaceous glands but also promoted the expression of Ki67, CK10, and CK14 in epidermal cells. MEBO had no significant effect on the differentiation process of keratinocytes.ConclusionOur study further proved that MEBO plays a positive role in diabetic wound healing, and its excellent ability to promote re-epithelialization may be an important reason for promoting wound healing.
| S-EPMC9871640 | biostudies-literature
Project description:The S100A2 protein is an important regulator of keratinocyte differentiation, but its role in wound healing remains unknown. We establish epithelial-specific S100A2 transgenic (TG) mice and study its role in wound repair using punch biopsy wounding assays. In line with the observed increase in proliferation and migration of S100A2-depleted human keratinocytes, mice expressing human S100A2 exhibit delayed cutaneous wound repair. This was accompanied by the reduction of re-epithelialization as well as a slow, attenuated response of Mcp1, Il6, Il1?, Cox2, and Tnf mRNA expression in the early phase. We also observed delayed Vegfa mRNA induction, a delayed enhancement of the Tgf?1-mediated alpha smooth muscle actin (?-Sma) axis and a differential expression of collagen type 1 and 3. The stress-activated p53 tumor suppressor protein plays an important role in cutaneous wound healing and is an S100A2 inducer. Notably, S100A2 complexes with p53, potentiates p53-mediated transcription and increases p53 expression both transcriptionally and posttranscriptionally. Consistent with a role of p53 in repressing NF-?B-mediated transcriptional activation, S100A2 enhanced p53-mediated promoter suppression of Cox2, an early inducible NF-?B target gene upon wound injury. Our study thus supports a model in which the p53-S100A2 positive feedback loop regulates wound repair process.
| S-EPMC5882638 | biostudies-literature
Project description:Clearance of p21-highly-expressing senescent cells accelerates cutaneous wound healing
| PRJNA1167732 | ENA
Project description:ANT2 accelerates cutaneous wound healing in aged skin by reverse senescence
| PRJNA849413 | ENA
Project description:To identify candidate genes involved in re-epithelialization of TGF-b induced dedifferentiated hRPTEC, this experiment was designed.
2016-04-01 | GSE74436 | GEO