A new mechanism in negative pressure wound therapy: interleukin-17 alters chromatin accessibility profiling

Area of Science:

• Wound Healing Research
• Molecular Biology
• Biomedical Engineering

Background:

• Negative pressure wound therapy (NPWT) is a widely used clinical treatment for enhancing wound healing.
• The precise molecular mechanisms underlying NPWT's efficacy remain incompletely understood.
• Investigating these mechanisms is crucial for optimizing therapeutic strategies.

Purpose of the Study:

• To elucidate the molecular mechanisms by which NPWT promotes wound healing.
• To investigate the role of the IL-17 signaling pathway in NPWT-mediated wound repair.
• To explore the impact of NPWT on chromatin accessibility in skin fibroblasts.

Main Methods:

• Establishment of rat skin wound-healing models with NPWT application.
• Immunofluorescence (IF) for vimentin, collagen I, and MMP9.
• RNA-sequencing (RNA-seq), Western blotting, quantitative PCR, and ATAC-seq for gene and protein expression and chromatin accessibility analysis.

Main Results:

• NPWT significantly promoted reepithelialization, extracellular matrix (ECM) synthesis, and proliferation in early-stage wound healing.
• Differentially expressed genes were enriched in the IL-17 signaling pathway, with IL-17 identified as upregulated by NPWT.
• Inhibition of IL-17 using secukinumab (SEC) abolished NPWT's beneficial effects; NPWT and IL-17 altered chromatin accessibility in fibroblasts.

Conclusions:

• NPWT upregulates IL-17 to promote wound healing, representing a novel mechanism.
• NPWT and IL-17 stimulation alter chromatin accessibility in skin fibroblasts.
• This study provides new insights into the molecular basis of NPWT's efficacy in wound repair.