Negative Pressure Wound Therapy Promotes Wound Healing by Inhibiting Inflammation in Diabetic Foot Wounds: A Role for NOD1 Receptor

Abstract

Aims: Diabetic foot results in frequent amputation and quality-of-life reduction in diabetes population. These lesions are featured by a prolonged and exaggerated inflammation with a significant impairment in local bacterial invasion. Negative pressure wound therapy (NPWT) attenuates hyperinflammation in the healing of diabetic foot wounds, but the potential mechanism of NPWT down-regulated inflammatory reaction still remains elusive. This study aims to explore the inflammatory signaling involved in the effect of NPWT on diabetic ulcer. Methods: Thirty patients with diabetic foot ulceration were divided into NPWT group (treated with NPWT, n = 10), NPWT + FK565 group (treated with NPWT combined with FK565 which is NOD1 receptor ligand, n = 10) and control group (n = 10). After two weeks treatment, samples were harvested and analyzed by histochemistry for infiltration of inflammatory cells, immunofluorescence stain for NOD1, western blotting for NOD1, RIP2 (Receptor interacting protein 2), IL-1β, TAK1 (Transforming growth factor-β-activated kinase1), p65 and real time-PCR for expression of NOD1 and RIP2. Results: NPWT could notably accelerate the diabetic wound healing through alleviating inflammatory reaction. The immunofluorescence analysis results revealed that NOD1 was mainly expressed in the cytoplasm and noticeably decreased after the NPWT treatment. And NPWT obviously decreased both the mRNA and protein level of NOD1 and RIP2. Moreover, The protein expression of IL-1β, TAK1 and p65 in the NPWT-group were significant decreased. Conclusion: NPWT effectively promotes wound healing by suppressing the wound inflammation in diabetic foot, which is mediated at least in part by suppression of NOD1 receptor.