Details

Autor(en) / Beteiligte

• Ludwig-Slomczynska, A H
• Borys, S
• Seweryn, M T
• Hohendorff, J
• Kapusta, P
• Kiec-Wilk, B
• Pitera, E
• Wolkow, P P
• Malecki, M T

Titel

DNA methylation analysis of negative pressure therapy effect in diabetic foot ulcers

Ist Teil von

• Endocrine Connections, 2019-11, Vol.8 (11), p.1474-1482

Ort / Verlag

England: Bioscientifica Ltd

Erscheinungsjahr

2019

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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 the inhibition of complement system activation.