GnRH impairs diabetic wound healing through enhanced NETosis
作者机构：Department of OtolaryngologySchool of MedicineAjou UniversitySuwonRepublic of Korea Department of Molecular Science and TechnologyAjou UniversitySuwonRepublic of Korea Department of OtolaryngologySchool of MedicineChungnam National UniversityDaejeonRepublic of Korea Department of Orthopedic SurgeryAjou UniversitySuwonRepublic of Korea
出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)
年 卷 期：2020年第17卷第8期
页 面：856-864页
核心收录：
学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学]
基 金：This study was supported by the National Research Foundation of Korea grant funded by the Korean government(MSIP)(No.2011-0030043(SRC)),(2017M3A9F7079339) the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT,and Future Planning(2018R1A2B3009008).
主 题：Neutrophils GnRH Diabetic wound healing NETosis
摘 要：It has been reported that neutrophil extracellular traps(NETs)impair wound healing in diabetes and that inhibiting NET generation(NETosis)improves wound healing in diabetic mice.Gonadotropin-releasing hormone(GnRH)agonists are associated with a greater risk of diabetes.However,the role of GnRH in diabetic wound healing is unclear.We determined whether GnRH-promoted NETosis and induced more severe and delayed diabetic wound healing.A mouse model of diabetes was established using five injections with streptozotocin.Mice with blood glucose levels250 mg/dL were then used in the experiments.GnRH agonist treatment induced delayed wound healing and increased NETosis at the skin wounds of diabetic mice.In contrast,GnRH antagonist treatment inhibited GnRH agonist-induced delayed wound healing.The expression of NETosis markers PAD4 and citrullinated histone H3 were increased in the GnRH-treated diabetic skin wounds in diabetic mice and patients.In vitro experiments also showed that neutrophils expressed a GnRH receptor and that GnRH agonist treatment increased NETosis markers and promoted phorbol myristate acetate(PMA)-induced NETosis in mouse and human neutrophils.Furthermore,GnRH antagonist treatment suppressed the expression of NETosis markers and PMA-induced NETosis,which were increased by GnRH treatment.These results indicated that GnRH-promoted NETosis and that increased NETosis induced delayed wound healing in diabetic skin wounds.Thus,inhibition of GnRH might be a novel treatment of diabetic foot ulcers.
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