Shiyan Li1, Xiaofeng Ding2, Hao Zhang3, Youjun Ding4, Qian Tan5. 1. Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, NO. 321, Zhongshan Road, Nanjing, Jiangsu, China. Electronic address: vincentnju@163.com. 2. Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, NO. 321, Zhongshan Road, Nanjing, Jiangsu, China. Electronic address: 814732113@qq.com. 3. Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, NO. 321, Zhongshan Road, Nanjing, Jiangsu, China. Electronic address: zhanghaoch@outlook.com. 4. Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, NO. 321, Zhongshan Road, Nanjing, Jiangsu, China. Electronic address: youjunding@126.com. 5. Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, NO. 321, Zhongshan Road, Nanjing, Jiangsu, China; Department of Burns and Plastic Surgery, Anqing Shihua Hospital, Nanjing Drum Tower Hospital Group, Anqing 246002, China. Electronic address: smmutanqian@sina.com.
Abstract
BACKGROUND: Persistent chronic inflammation is one of the main pathogenic characteristics of diabetic wounds. The resolution of inflammation is important for wound healing and extracellular matrix (ECM) formation. Interleukin (IL)-25 can modulate the function of macrophage and fibroblast, but its role and mechanism of action in the treatment of diabetic wounds remain largely unclear. METHODS: The mice were categorized into diabetic, diabetic + IL-25 and control groups. Human monocytic THP-1 cell line and human dermal fibroblast (HDF) were stimulated under different IL-25 conditions. Then, flow cytometry, real-time quantitative PCR (RT-qPCR), Western blot (WB), and immunofluorescence (IF) assays were carried out. RESULTS: The mice in diabetes group (DG) had a slower wound healing rate, more severe inflammation, less blood vessels and more disordered collagen than those in control group (CG). Intradermal injection of IL-25 could improve these conditions. IL-25 promoted M2 macrophage polarization and fibroblast activation in DG and high-glucose environment. The phenomenon, which was dependent on PI3K/AKT/mTOR and TGF-β/SMAD signaling, could be blocked by LY294002 and LY2109761. CONCLUSION: IL-25 may serve as a therapeutic target to improve wound healing in diabetic mice.
BACKGROUND: Persistent chronic inflammation is one of the main pathogenic characteristics of diabetic wounds. The resolution of inflammation is important for wound healing and extracellular matrix (ECM) formation. Interleukin (IL)-25 can modulate the function of macrophage and fibroblast, but its role and mechanism of action in the treatment of diabetic wounds remain largely unclear. METHODS: The mice were categorized into diabetic, diabetic + IL-25 and control groups. Human monocytic THP-1 cell line and human dermal fibroblast (HDF) were stimulated under different IL-25 conditions. Then, flow cytometry, real-time quantitative PCR (RT-qPCR), Western blot (WB), and immunofluorescence (IF) assays were carried out. RESULTS: The mice in diabetes group (DG) had a slower wound healing rate, more severe inflammation, less blood vessels and more disordered collagen than those in control group (CG). Intradermal injection of IL-25 could improve these conditions. IL-25 promoted M2 macrophage polarization and fibroblast activation in DG and high-glucose environment. The phenomenon, which was dependent on PI3K/AKT/mTOR and TGF-β/SMAD signaling, could be blocked by LY294002 and LY2109761. CONCLUSION: IL-25 may serve as a therapeutic target to improve wound healing in diabetic mice.
Authors: Maryam Sharifiaghdam; Elnaz Shaabani; Reza Faridi-Majidi; Stefaan C De Smedt; Kevin Braeckmans; Juan C Fraire Journal: Mol Ther Date: 2022-08-02 Impact factor: 12.910