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黄金梅 唐 婷 韦柳叶 付 军 唐乾利 ＨＵＡＮＧ Ｊｉｎｍｅｉ， ＴＡＮＧ Ｔｉｎｇ， ＷＥＩ Ｌｉｕｙｅ， ＦＵ Ｊｕｎ， ＴＡＮＧ Ｑｉａｎｌｉ
基金项目： 国家自然科学基金面上项目 （８１７７４３２７）； “广西特聘专家” 专项经费资助项目 （桂人才通字 ［２０１９］ １３ 号）； 广西 医学高层次领军人才培养 “１３９” 计划资助项目 （桂卫科教发 ［２０１８］ ２２ 号） 作者单位： ５３０００１ 广西 南宁， 广西中医药大学研究生院 ２０２０ 级中医外科专业 （黄金梅， 唐婷， 韦柳叶）； ５３００２３ 广西 南宁， 广西中医药大学第一附属医院肛肠外科 （付军）； ５３３０００ 广西 百色， 右江民族医学院／ 桂西高发病防治重 点实验室 （唐乾利） 通信作者： 唐乾利， Ｅｍａｉｌ： ｈｔｍｇｘ＠ １６３
Fang Zhang1,2, Ye Liu2 , Shiqi Wang1 , Xin Yan1 , Yue Lin1 , Deyan Chen2*, Qian Tan1* and Zhiwei Wu2,3,4*
1 Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China, 2 Center for Public Health Research, Medical School, Nanjing University, Nanjing, China, 3 State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, China, 4 Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, China.
Diabetic foot ulcer (DFU) frequently leads to non-traumatic amputation and finally even death. However, the mechanism of DFU is not fully understood. Interleukin 25 (IL-25), an alarmin cytokine that responds to tissue injury, has been reported to participate in tissue regeneration and maintaining glucose homeostasis. However, the role of IL-25 in diabetic wound healing remains unknown. Here, we showed that interleukin 17 receptor B (IL- 17RB), the functional receptor of IL-25, was significantly inhibited in the wound skin of both diabetic patients with DFU and streptozotocin (STZ)-induced diabetic mice. Topical administration of recombinant IL-25 protein improved angiogenesis and collagen deposition in the wound bed and thus ameliorated delayed diabetic wound healing. IL- 25 increased endothelial-specific CD31 expression in diabetic wounds and exogenous IL- 25 protected endothelial cells from high glucose-impaired cell migration and tube formation in vitro. We further revealed that IL-25-mediated-IL-17RB signaling rescued the downregulation of Wnt/b-catenin pathway both in vivo in diabetic mice and in vitro in HUVECs and induced the phosphorylation of AKT and ERK 1/2 in HUVECs under high glucose conditions. This study defines a positive regulatory role of IL-25-mediated-IL- 17RB signaling in diabetic wound healing and suggests that induction of IL-25-mediated IL-17RB signaling may be a novel therapeutic strategy for treating poor healing diabetic wounds.
Keywords: IL-25, IL-17RB, diabetes mellitus, wound healing, endothelial cell functions.
Elif Aydın1, Mustafa Bülent Ertuğrul2
1 Department of Physical Medicine and Rehabilitation, Adnan Menderes University, Faculty of Medicine, Aydın, Turkey
2 Department of Infectious Diseases and Clinical Microbiology, Reyap Hospital, Istanbul, Turkey
Received: March 19, 2021 Accepted: August 17, 2021 Published online: December 01, 2021
ABSTRACT
Diabetes is one of the most common health problems worldwide. Diabetic foot wounds (DFWs) are hazardous complications of the disease. Patients are often referred to rehabilitation facilities at later stages of the diabetic complications, particularly after amputation surgery. There are potential benefits of rehabilitation practices in preventing and managing DFWs. Therefore, rehabilitation needs to be more involved in the management of DFWs and should be in all stages of diabetic care. In this review, we discuss literature data to bring rehabilitation perspective to the multidisciplinary management of DFWs.
Keywords: Diabetic foot, exercise, foot ulceration, plantar pressure, rehabilitation.
