Research Paper Volume 13, Issue 8 pp 12143—12159
Effects of advanced glycation end products on neutrophil migration and aggregation in diabetic wounds
- 1 Department of Burn, Shanghai Jiao Tong University Affiliated Ruijin Hospital, Shanghai, China
- 2 Department of Rheumatology and Immunology, Shanghai Jiao Tong University Affiliated Ruijin Hospital, Shanghai, China
Received: November 5, 2020 Accepted: March 14, 2021 Published: April 26, 2021
https://doi.org/10.18632/aging.202924How to Cite
Copyright: © 2021 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Increased accumulation of advanced glycation end products (AGEs) in diabetic skin is closely related to delayed wound healing. Studies have shown that the concentration of AGEs is elevated in the skin tissues and not subcutaneous tissues in refractory diabetic wounds, which suggests there may be a causal relationship between the two. In the present study, in vitro experiments revealed that AGEs activated neutrophils, and the migratory and adhesive functions of neutrophils decreased once AGE levels reached a certain threshold. Different levels of AGE expression differentially affected the function of neutrophils. Messenger RNA (mRNA) sequencing analysis combined with real-time polymerase chain reaction (PCR) showed that poliovirus receptor (PVR/CD155) and CTNND1, which play a role in migration- and adhesion-related signaling pathways, were decreased following AGE stimulation. Consequently, neutrophils cannot effectively stimulate the formation of the inflammatory belt needed to remove necrotic tissues and defend against foreign microorganisms within diabetic chronic wounds. In addition, this phenomenon may be related to the differential accumulation of AGEs in different layers of the skin.