IL-25 通过刺激 M2 巨噬细胞极化和成纤维细胞活化来改善糖尿病创面愈合。
IL-25 improves diabetic wound healing through stimulating M2 macrophage polarization and fibroblast activation.
机构信息
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, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, NO. 321, Zhongshan Road, Nanjing, Jiangsu, China.
出版信息
Int Immunopharmacol. 2022 May;106:108605. doi: 10.1016/j.intimp.2022.108605. Epub 2022 Feb 8.
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.
背景
持续性慢性炎症是糖尿病伤口的主要发病特征之一。炎症的消退对于伤口愈合和细胞外基质（ECM）的形成很重要。白细胞介素（IL）-25 可以调节巨噬细胞和成纤维细胞的功能，但它在治疗糖尿病伤口中的作用和机制在很大程度上仍不清楚。
方法
将小鼠分为糖尿病组、糖尿病+IL-25 组和对照组。在不同 IL-25 条件下刺激人单核细胞 THP-1 细胞系和人真皮成纤维细胞（HDF）。然后进行流式细胞术、实时定量 PCR（RT-qPCR）、Western blot（WB）和免疫荧光（IF）检测。
结果
糖尿病组（DG）的小鼠伤口愈合速度较慢，炎症更严重，血管较少，胶原排列更紊乱，与对照组（CG）相比。皮内注射 IL-25 可以改善这些情况。IL-25 可促进 DG 和高糖环境中 M2 巨噬细胞极化和成纤维细胞激活。该现象依赖于 PI3K/AKT/mTOR 和 TGF-β/SMAD 信号通路，可以被 LY294002 和 LY2109761 阻断。
结论
IL-25 可能成为改善糖尿病小鼠伤口愈合的治疗靶点。
Zotero 插件