The Epigenetics of Negative Pressure Wound Therapy? DNA Methylation and healing of diabetic foot ulcers #NPWT #ActAgainstAmputation #DiabeticFoot

Fascinating and potentially impactful work from colleagues from Krakow regarding analysis and reporting of DNA methylation during NPWT.

OBJECTIVE:

Negative pressure wound therapy (NPWT) has been used to treat diabetic foot ulcerations (DFUs). Its action on the molecular level, however, is only partially understood. Some earlier data suggested NPWT may be mediated through modification of local gene expression. As methylation is a key epigenetic regulatory mechanism of gene expression, we assessed the effect of NPWT on its profile in patients with type 2 diabetes (T2DM) and neuropathic non-infected DFUs.

METHODS:

Of 36 included patients, 23 were assigned to NPWT and 13 to standard therapy. Due to ethical concerns, the assignment was non-randomized and based on wound characteristics. Tissue samples were obtained before and 8±1 days after therapy initiation. DNA methylation patterns were checked by Illumina Methylation EPIC kit.

RESULTS:

In terms of clinical characteristics, the groups presented typical features of T2DM; however, the NPWT group had significantly greater wound area: 16.8 cm2 vs. 1.4 cm2 (p=0.0003). Initially only one region at chromosome 5 was differentially methylated. After treatment, 57 differentially methylated genes were found, mainly located on chromosomes 6 (chr6p21) and 20 (chr20p13); they were associated with DNA repair and autocrine signaling via retinoic acid receptor. We performed differential analyses pre-treatment and post-treatment. The analysis revealed 426 differentially methylated regions in the NPWT group, but none in the control group. The enrichment analysis showed 11 processes significantly associated with NPWT, of which 4 were linked with complement system activation. All but one were hypermethylated after NPWT.

CONCLUSION:

The NPWT effect on DFUs may be mediated through epigenetic changes resulting in inhibition of complement system activation.

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