Traumatic Brain Injury Induces Early Barrier Protective Responses in Incisional Skin Wounds Accelerating Cutaneous Wound Healing
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ABSTRACT:
PROVIDER: PRJNA1218650 | ENA |
REPOSITORIES: ENA
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Project description:Though Traumatic Brain Injury (TBI) and skin trauma often occur together, it is unresolved whether TBI changes healing of skin wounds. We here explored whether TBI impacts on the sequence of events during skin wound healing. Incisional skin wounds from mice subjected to TBI were assessed employing unbiased transcriptome analysis and immunostaining. Transcriptome analysis at day 1 after combined trauma detects a significant enrichment of genes involved in macrophage and T cell recruitment and activation in contrast to skin wounds without TBI. At day 7 after combined trauma, genes in pathways of re-epithelialization including cornification and keratinization and of anti-inflammatory responses were highly enriched. These findings were confirmed by immunostaining with increased re-epithelialisation and cornification and an increased number of macrophages and T cells resolving inflammation. Moreover, the number of dermal myofibroblasts are highly increased in skin wounds after combined trauma. Collectively, TBI enforces an unprecedented defence response with an early onset of enhanced immunity, faster epidermal barrier formation, and a myofibroblast driven acceleration of wounds closure, all together likely counteracting systemic infection.
2025-09-03 | GSE288594 | GEO
Project description:Adalimumab is the only FDA- and EMA-approved treatment for moderate-to-severe hidradenitis suppurativa (HS), suggesting that the mechanism of action of adalimumab is distinct in HS and may contribute to improved wound healing. We have demonstrated that adalimumab, but neither etanercept nor certolizumab-pegol, induces a wound healing profile in vitro, which may underlie the differences in efficacy between various anti-TNF agents. To examine and compare the efficacy of therapeutic TNF inhibitors in chronic cutaneous wound healing in vivo, a human TNF knock-in Leprdb/db mouse model was established. The vehicle group exhibited severe impairments in cutaneous wound healing. In contrast, adalimumab significantly accelerated healing, confirmed by both histologic assessment and a unique healing transcriptional profile. Moreover, adalimumab and infliximab showed similar levels of efficacy, but golimumab was less effective, along with etanercept and certolizumab-pegol. In line with histologic assessments, proteomics analyses from healing wounds exposed to various TNF inhibitors revealed distinct and differential wound healing signatures that may underlie the differential efficacy of therapeutic inhibitors in accelerating chronic wound healing.
2023-09-11 | PXD040275 | Pride
Project description:Adalimumab, but neither etanercept nor certolizumab-pegol, has been reported to induce a wound healing profile in the circulation of patients with hidradenitis suppurativa (HS), a chronic inflammatory skin disease. However, the role of tumor necrosis factor alpha (TNF) inhibitors in cutaneous wound healing in vivo is still unclear. To examine and compare the efficacy of various TNF inhibitors in cutaneous wound healing in vivo, a human TNF knock-in Leprdb/db mouse model was established to model the impaired cutaneous wound healing as seen in HS. The vehicle group exhibited severe impairments in cutaneous wound healing. In contrast, adalimumab significantly accelerated healing, confirmed by both histologic assessment and a unique healing transcriptional profile. Moreover, adalimumab and infliximab showed similar levels of efficacy, but golimumab was less effective, along with etanercept and certolizumab-pegol. In line with histologic assessments, proteomics analyses from healing wounds exposed to various TNF inhibitors revealed distinct and differential wound healing signatures that may underlie the differential efficacy of these inhibitors in accelerating cutaneous wound healing. Taken together, these data revealed that TNF inhibitors exhibited differential levels of efficacy in accelerating cutaneous wound healing in the impaired wound healing model in vivo likely through distinct mechanisms of action related to the structure of the biologic or its ability to bind TNF.
2023-09-11 | GSE242837 | GEO
Project description:Using microarray analysis, we explored the differences in gene expression in wounded and intact skin using murine model. Injured skin samples were examined at days 1 and 4 post injury. The results provide the detailed molecular profile of the the genetic response to injury. Two full-thickness dermal wounds were made on the opposite sides of the midline of each mouse using a 4 mm punch biopsy instrument. Wounds were made through the epidermis, dermis, and subcutaneous tissue layers while leaving the fascia intact. At a specified time point after the wounding (1 and 4 days), mice were sacrificed by carbon dioxide inhalation. The wounds and surrounding tissues or intact skin samples were removed with an 8 mm biopsy punch.
2015-12-19 | E-GEOD-76144 | biostudies-arrayexpress
Project description:Among the initial responses to skin injury, triggering inflammatory mediators and modifying oxidative status provide the necessary temple for the subsequent output of a new functional barrier, fibroplasia and collagen deposition, modulated by NF-κB and TGF-β1 expressions. Hence, the current study aimed to investigate the effect of local application of ursodeoxycholic acid (UDCA) on cutaneous wound healing induced in Swiss mice. Wound contraction progression was monitored by daily photographing the wounds. Enhanced fibroblast cell migration was observed after incubation with UDCA. Topical application of UDCA (500 μM) cream on excised wounds significantly enhanced wound contraction and improved morphometric scores. In addition, UDCA ameliorated the unbalanced oxidative status of granulated skin tissues. Interestingly, it showed increased expression of TGF-β1 and MMP-2 with decreased expression of NF-κB. On the other hand, UDCA significantly increased collagen fibers deposition and hydroxyproline content and enhanced re-epithelization. UDCA also modified the mitochondrial function throughout the healing process, marked by lower consumption rates of mitochondrial ATP, complex I contents as well as intracellular NAD+ contents accompanied by elevated levels of nicotinamide compared to the untreated controls. In chronic gamma-irradiated (6Gy) model, the illustrated data showed enhanced wound contraction via increased TGF-β1/MMP-2 and collagen deposition incurred by topical application of UDCA without effect on NF-κB level. In sum, the present findings suggest that UDCA may accelerate wound healing by regulating TGF-β1 and MMP-2 and fibroplasia/collagen deposition in either the two wound healing models.
| S-EPMC6927640 | biostudies-literature
Project description:The aim of this experiment was measure the influence of age on cutaneous wound healing using human subjects. Increaded age has been associated with delayed wound healing in mouse models and in humans. Gene expression was compared between excisional biopsy wounds from young and old subjects.
2008-04-10 | E-MEXP-1074 | biostudies-arrayexpress
Project description:Ageing-related delays in wound healing are well-documented in both human and animal models. However, the mechanisms underlying this impairment in healing progression are not fully understood. In this study, we characterised ageing-associated changes to the structure and function of the skin in young and aged mice and investigated the cellular differences that impacted the progression of wound healing. Full-thickness wounds created on the dorsum of C57BL/6J young and aged mice were excised on Day 0, Day 3 and Day 7 post-wounding for analysis by immunohistochemistry, flow cytometry, RNA sequencing. Our data revealed that macrophages were significantly reduced in aged wounds in comparison to young. Functional transcriptomic analyses showed that macrophages from aged wounds exhibited significantly reduced expression of cell cycle, DNA replication, and repair pathway genes. Furthermore, we uncovered an elevated pro-inflammatory gene expression program in the aged macrophages linked to poor inflammation resolution and excessive tissue damage observed in aged wounds. Altogether, our work provides insights into how poorly healing aged wounds are phenotypically defined by the presence of macrophages with reduced proliferative capacity and an exacerbated inflammatory response, both of which are pathways that can be targeted to improve healing in the elderly.
2022-06-24 | GSE199763 | GEO
Project description:Therapeutic TNF Inhibitors Exhibit Differential Levels of Efficacy in Accelerating Cutaneous Wound Healing
| PRJNA1015129 | ENA
Project description:To study early-onset gene expression changes in cutaneous wound healing, 3 mm wounds were induced into the back skin of female wildtype C57BL/6 mice using a biopsy punch. Mice were sacrificed 2h, 6h or 24h post wound induction (PWI) and 1 - 1.5 mm of skin lining the wound edge was isolated and sequenced. The skin from the initial punch biopsy (0h PWI) was preserved and taken as a control sample to identify differentially expressed genes.
2018-07-31 | E-MTAB-6686 | biostudies-arrayexpress
Project description:Adalimumab but neither etanercept nor certolizumab-pegol has been reported to induce a wound-healing profile in vitro by regulating macrophage differentiation and matrix metalloproteinase expression, which may underlie the differences in efficacy between various TNF-α inhibitors in impaired wound healing in patients with hidradenitis suppurativa, a chronic inflammatory skin disease. To examine and compare the efficacy of various TNF inhibitors in cutaneous wound healing in vivo, a human TNF knock-in Leprdb/db mouse model was established to model the impaired cutaneous wound healing as seen in hidradenitis suppurativa. The vehicle group exhibited severe impairments in cutaneous wound healing. In contrast, adalimumab significantly accelerated healing, confirmed by both histologic assessment and a unique healing transcriptional profile. Moreover, adalimumab and infliximab showed similar levels of efficacy, but golimumab was less effective, along with etanercept and certolizumab-pegol. In line with histologic assessments, proteomics analyses from healing wounds exposed to various TNF inhibitors revealed distinct and differential wound-healing signatures that may underlie the differential efficacy of these inhibitors in accelerating cutaneous wound healing. Taken together, these data revealed that TNF inhibitors exhibited differential levels of efficacy in accelerating cutaneous wound healing in the impaired wound-healing model in vivo.
| S-EPMC10788510 | biostudies-literature