Advanced glycation end products regulate macrophage apoptosis and influence the healing of diabetic foot wound through miR-361-3p/CSF1R and PI3K/AKT pathway

Yongzhi Jin; Yi Huang; Guang Zeng; Junsheng Hu; Mengfan Li; Ming Tian; Tao Lei; Rong Huang

Heliyon (Jan 2024)

Advanced glycation end products regulate macrophage apoptosis and influence the healing of diabetic foot wound through miR-361-3p/CSF1R and PI3K/AKT pathway

Yongzhi Jin,
Yi Huang,
Guang Zeng,
Junsheng Hu,
Mengfan Li,
Ming Tian,
Tao Lei,
Rong Huang

Affiliations

Yongzhi Jin: Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
Yi Huang: Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
Guang Zeng: Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
Junsheng Hu: Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China
Mengfan Li: Department of General Surgery, LiQun Hospital, Shanghai, 200333, China
Ming Tian: Shanghai Burn Institute, Department of Burn, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China; Corresponding author.
Tao Lei: Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China; Corresponding author.
Rong Huang: Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China; Corresponding author. Department of General Surgery, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 Lanxi Rd, Shanghai, 200062, China.

Journal volume & issue: Vol. 10, no. 2
p. e24598

Abstract

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Background: Diabetic foot ulcers (DFUs) are a severe complication of diabetes. Persistent inflammation and impaired vascularization present considerable challenges in tissue wound healing. The aim of this study was to identify the crucial regulators of DFU wound healing and investigate their specific mechanisms in DFU. Methods: DFU RNA sequencing data were obtained to identify crucial feature genes. The expression levels of the feature genes and their corresponding microRNAs (miRNAs) were verified in clinical samples. Subsequently, the expression of CD68 was determined in DFU and non-diabetic foot skin samples. RAW 264.7 cells were treated with advanced glycation end products (AGEs) to determine their viability and apoptosis. Finally, the roles of the selected crucial genes and their corresponding miRNAs were investigated using in vitro experiments and a mouse model of diabetes. Results: Bioinformatic analysis showed that five crucial feature genes (CORO1A, CSF1R, CTSH, NFE2L3, and SLC16A10) were associated with DFU wound healing. The expression validation showed that miR-361-3p-CSF1R had a significant negative correlation and was thus selected for further experiments. AGEs significantly inhibited the viability of RAW 264.7 cells and enhanced their apoptosis; furthermore, the AGEs significantly downregulated CSF1R and increased miR-361-3p levels compared with the control cells. Additionally, inhibition of miR-361-3p decreased the cell apoptosis caused by AGEs and increased the levels of p-AKT/AKT and p-PI3K/PI3K, whereas CSF1R knockdown reversed the effects of miR-361-3p. In vivo experiments showed that miR-361-3p inhibition promoted wound healing in diabetic mice and regulated PI3K/AKT levels. Conclusions: AGEs may regulate macrophage apoptosis via the miR-361-3p/CSF1R axis and PI3K/AKT pathway, thereby influencing DFU wound healing.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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