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Topical TWEAK Accelerates Healing of Experimental Burn Wounds in Mice.

ABSTRACT: The interaction of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (Fn14) participates in inflammatory responses, fibrosis, and tissue remodeling, which are central in the repair processes of wounds. Fn14 is expressed in main skin cells including dermal fibroblasts. This study was designed to explore the therapeutic effect of TWEAK on experimental burn wounds and the relevant mechanism underlying such function. Third-degree burns were introduced in two BALB/c mouse strains. Recombinant TWEAK was administrated topically, followed by the evaluation of wound areas and histologic changes. Accordingly, the downstream cytokines, inflammatory cell infiltration, and extracellular matrix synthesis were examined in lesional tissue. Moreover, the differentiation markers were analyzed in cultured human dermal fibroblasts upon TWEAK stimulation. The results showed that topical TWEAK accelerated the healing of burn wounds in wild-type mice but not in Fn14-deficient mice. TWEAK strengthened inflammatory cell infiltration, and exaggerated the production of growth factor and extracellular matrix components in wound areas of wild-type mice. Moreover, TWEAK/Fn14 activation elevated the expression of myofibroblastic differentiation markers, including alpha-smooth muscle actin and palladin, in cultured dermal fibroblasts. Therefore, topical TWEAK exhibits therapeutic effect on experimental burn wounds through favoring regional inflammation, cytokine production, and extracellular matrix synthesis. TWEAK/Fn14 activation induces the myofibroblastic differentiation of dermal fibroblasts, partially contributing to the healing of burn wounds.

SUBMITTER: Liu J

PROVIDER: S-EPMC6021523 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Topical TWEAK Accelerates Healing of Experimental Burn Wounds in Mice.

Liu Jing J Peng Lingling L Liu Yale Y Wu Kunyi K Wang Sijia S Wang Xuening X Liu Qilu Q Xia Yumin Y Zeng Weihui W

Frontiers in pharmacology 20180621

The interaction of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (Fn14) participates in inflammatory responses, fibrosis, and tissue remodeling, which are central in the repair processes of wounds. Fn14 is expressed in main skin cells including dermal fibroblasts. This study was designed to explore the therapeutic effect of TWEAK on experimental burn wounds and the relevant mechanism underlying such function. Third-degree burn ...[more]

PMID: 29977207

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Project description:IntroductionTopical wound treatments rely on carrier formulations with little to no biological impact. The potential for a common vehicle, a propylene glycol (PG) gel, to affect wound healing measures including microbiota is not known. Microbiome characterization, based on next generation sequencing methods is typically performed on tissue or directly obtained wound fluid samples. The utility for primary wound dressings to characterize equine wound microbiota in the context of topical treatments is currently unknown. This investigation reports the topical effect of an 80% PG based gel on wound healing and microbiota in wound dressings.MethodsExperiments were performed in six mature horses utilizing a surgical, distal limb wound model, histology of sequential wound biopsies, photographic wound measurements and microbiota profiling via 16s rRNA sequencing of wound dressing samples. Experimental wounds were surveyed for 42 days and either treated (Day 7, 14, 21 and 28; at 0.03 ml/cm2) or unexposed to the PG gel. Wound surface area, relative and absolute microbial abundances, diversity indices and histologic parameters were analyzed in the context of the experimental group (treatment; control) using qualitative or quantitative methods depending on data characteristics.ResultsCompared to controls, treatment slowed the wound healing rate (17.17 ± 4.27 vs. 18.56 ± 6.3 mm2/day), delayed the temporal decline of polymorphonucleated cells in wound beds and operational taxonomic units (OTU) in wound dressings and lowered alpha-diversity indices for microbiota in primary wound dressing. Relative abundances of OTUs were in line with those previously reported for equine wounds. Clinical outcomes 42 days post wounding were considered similar irrespective of PG gel exposure.DiscussionResults highlight the potential for vehicle exposure to alter relevant wound outcome measures, imposing the need for stringent experimental control measures. Primary wound dressings may represent an alternate sample source for characterization of the wound microbiome alleviating the need for additional interventions. Further studies are warranted to contrast the microbiome in wound dressings against that present on wound surfaces to conclude on the validity of this approach.

Project description:Background Wound healing involves careful coordination among various cell types carrying out unique or even multifaceted functions. The abstraction of this complex dynamic process into four primary wound stages is essential to the study of wound care for timing treatment and tracking wound progression. For example, a treatment that may promote healing in the inflammatory stage may prove detrimental in the proliferative stage. Additionally, the time scale of individual responses varies widely across and within the same species. Therefore, a robust method to assess wound stages can help advance translational work from animals to humans. Results In this work, we present a data-driven model that robustly identifies the dominant wound healing stage using transcriptomic data from biopsies gathered from mouse and human wounds, both burn and surgical. A training dataset composed of publicly available transcriptomic arrays is used to derive 58 shared genes that are commonly differentially expressed. They are divided into 5 clusters based on temporal gene expression dynamics. The clusters represent a 5-dimensional parametric space containing the wound healing trajectory. We then create a mathematical classification algorithm in the 5-dimensional space and demonstrate that it can distinguish between the four stages of wound healing: hemostasis, inflammation, proliferation, and remodeling. Conclusions In this work, we present an algorithm for wound stage detection based on gene expression. This work suggests that there are universal characteristics of gene expression in wound healing stages despite the seeming disparities across species and wounds. Our algorithm performs well for human and mouse wounds of both burn and surgical types. The algorithm has the potential to serve as a diagnostic tool that can advance precision wound care by providing a way of tracking wound healing progression with more accuracy and finer temporal resolution compared to visual indicators. This increases the potential for preventive action. Supplementary Information The online version contains supplementary material available at 10.1186/s12859-023-05295-z.

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Topical TWEAK Accelerates Healing of Experimental Burn Wounds in Mice.

Publications

Topical TWEAK Accelerates Healing of Experimental Burn Wounds in Mice.

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