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Effect of topical treatment with either lung surfactant or selective MMP inhibitor on excisional wounds in mice

ABSTRACT: Effect of topical treatment with either lung surfactant or selective MMP inhibitor on excisional wounds in mice

PROVIDER: PRJNA433684 | ENA |

REPOSITORIES: ENA

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Effect of topical treatment with either lung surfactant or selective MMP inhibitor on excisional wounds in mice

Project description:The aim of the study was to investigate the effect of bovine lung surfactant or selective MMP inhibition on skin wound healing. Excisional wounds were treated in one subpart of the study with Alveofact or control and in the other with a selective MMP-3 inhibitor UK 370106 in different concentrations. Lung surfactant and selective MMP-3 inhibitor reduced expression of pro-inflammatory mediators. Lung surfactant treatment activated genes for cell migration and against fibrosis.

2018-04-01 | GSE110438 | GEO

Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HDFa]

Project description:The management of antibiotic-resistant, bacterial biofilm infections in chronic skin wounds is a significant clinical challenge. Despite advances in diagnosis, many patients do not derive benefit from current anti-infective/antibiotic therapies. Here we report a novel class of epoxy-tiglianes and demonstrate their antimicrobial activity (modifying bacterial growth and inducing biofilm disruption), with structure/activity relationships established against important human pathogens. In vitro, the lead candidate, EBC-1013 stimulated PKC-dependent neutrophil ROS induction and NETosis, and increased expression of wound healing associated cytokines, chemokines and antimicrobial peptides in keratinocytes and fibroblasts. In vivo, topical EBC-1013 induced rapid resolution of infection with increased matrix remodelling in acute thermal injuries. In chronically-infected, diabetic wounds, treatment induced cytokine/chemokine production, inflammatory cell recruitment and complete healing (in 6/7 wounds) with ordered keratinocyte differentiation. These results highlight a non-antibiotic approach involving contrasting, orthogonal mechanisms of action: targeted biofilm disruption and innate immune induction in the treatment of chronic wounds.

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Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HEKa]

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Pharmacological YAP activation promotes regenerative repair of cutaneous wounds.

Project description:Chronic cutaneous wounds remain a persistent unmet medical need that decrease expectancy and quality of life. Here, we report that topical application of PY-60, a small molecule activator of the transcriptional coactivator YAP, promotes regenerative repair of cutaneous wounds in pig and human models. Pharmacological YAP activation enacts a reversible pro-proliferative transcriptional program in keratinocytes and dermal cells that results in accelerated re-epithelization and regranulation of the wound bed. These results demonstrate that transient topical administration of a YAP activating agent may represent a generalizable therapeutic approach to treating chronic wounds.

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Circular RNA expression profiling in diabetic foot ulcers and human normal acute wounds

Project description:Circular RNA (circRNA) microarray analysis was performed to examine the expression profiles of circRNAs in diabetic foot ulcers (DFU) and in human excisional skin wounds 7 days after injury.

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Wound healing and hair follicle regeneration with topical BRAF inhibitor therapy in a diabetic model

Project description:Wound healing is a multi-step process to rapidly restore barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Herein, we investigated whether this wound healing acceleration also occurs in impaired diabetic wounds and found that topical vemurafenib not only improves wound healing in a murine diabetic wound model, but unexpectedly promotes hair follicle regeneration. Neogenic hair follicles expressing Sox-9, CD34 and K15 were found in wounds of diabetic and non-diabetic mice, and their formation can be prevented by blocking downstream MEK signaling. Thus, topically applied BRAF inhibitors may accelerate wound healing, and promote the restoration of improved skin architecture in both normal and impaired wounds.

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Transcription profiling by array of excisional biopsy wounds from young and old human subjects to measure the influence of age on cutaneous wound healing

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.

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Gene expression profile at single cell level from untreated and Enterococcus faecalis-infected skin wounds

Project description:Enterococcus faecalis (E. faecalis) is a Gram-(+) opportunistic pathogen associated with predominantly nosocomial wound infections. E. faecalis has been shown to suppress or evade immune-mediated clearance by the immune system and promote persistent infection. Here, we sought to interrogate whether E. faecalis infection induces transcriptomic changes in the host at the single-cell resolution using a mouse excisional wound model. Keratinocyte, fibroblast, endothelial and immune cell populations reveal unique clusters in the infected wounds. Cell communication analysis discovered strong ligand-receptor interactions between macrophages and endothelial cells in the infected niche, whilst fibroblast and keratinocytes instruct healing cellular interactions in untreated skin wounds. We also identified differential terminal lineage driving genes, following RNA velocity in each condition. Together, results suggest that E. faecalis infection alters the skin transcriptome, which may help promote the chronicity of bacteria-infected wounds.

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Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HEKa]

Project description:Topical, immunomodulatory epoxy-tiglianes induce biofilm disruption and healing in acute and chronic skin wounds [HEKa]

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