One-quarter of people with diabetes suffer from diabetic foot ulcers (DFUs), a life-threatening complication of diabetes mellitus. DFUs are characterized by uncontrolled inflammation with decreased neutrophils due to loss of a transcription factor, FOXM1, and the formation of neutrophil extracellular traps (NETs). This report demonstrated reduced expression of TREM1, a neutrophil-specific regulator that amplifies inflammation, in DFUs. This study also described a novel pathway for regulating NET formation during diabetic wound healing through TREM1/FOXM1. As a result, the findings of this study will contribute to the development of more effective therapeutic strategies for patients with DFUs.

What is exciting about this article?

This report provides new insights into the role of the immune cell response in patients with DFUs and highlights the clinical relevance of signaling pathways that regulate NET formation during diabetic wound healing. The findings of this study correlate clinical outcomes in DFU patients with their molecular profile and indicate the potential for using therapeutics to target specific signals in these patients to reprogram nonhealing DFUs into healing competent DFU.

How does this fit into the larger NIAMS portfolio?

This study addresses a significant clinical problem associated with DFUs and sheds light on the cause of chronic wounds to advance an area of research that is poorly understood. In the future, this report may provide novel solutions to treat DFUs and other chronic skin wounds.

Grant support


Research Areas:

Developmental Biology Immunology Molecular Biology and Biochemistry Skin Biology


FOXM1 network in association with TREM1 suppression regulates NET formation in diabetic foot ulcers.

Sawaya AP, Stone RC, Mehdizadeh S, Pastar I, Worrell S, Balukoff NC, Kaplan MJ, Tomic-Canic M, Morasso MI
2022 Aug 3;
doi: 10.15252/embr.202154558
PMID: 35856334

Research reported in this publication was supported by the Intramural Research Program of the NIHʼs National Institute of Arthritis and Musculoskeletal and Skin Diseases.