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Neutrophil extracellular traps as a unique target in the treatment of chemotherapy-induced peripheral neuropathyResearch in context

التفاصيل البيبلوغرافية
العنوان: Neutrophil extracellular traps as a unique target in the treatment of chemotherapy-induced peripheral neuropathyResearch in context
المؤلفون: Chao-Yu Wang, Tong-Tong Lin, Liang Hu, Chen-Jie Xu, Fan Hu, Li Wan, Xing Yang, Xue-Feng Wu, Xiao-Tao Zhang, Yan Li, Hao-Yuan Yin, Chun-Yi Jiang, Hong-Liang Xin, Wen-Tao Liu
المصدر: EBioMedicine, Vol 90, Iss , Pp 104499- (2023)
بيانات النشر: Elsevier, 2023.
سنة النشر: 2023
المجموعة: LCC:Medicine
LCC:Medicine (General)
مصطلحات موضوعية: Chemotherapy-induced peripheral neuropathy, Neutrophil extracellular traps, Microcirculatory disturbance, SHp-DNase1, Medicine, Medicine (General), R5-920
الوصف: Summary: Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a severe dose-limiting side effect of chemotherapy and remains a huge clinical challenge. Here, we explore the role of microcirculation hypoxia induced by neutrophil extracellular traps (NETs) in the development of CIPN and look for potential treatment. Methods: The expression of NETs in plasma and dorsal root ganglion (DRG) are examined by ELISA, IHC, IF and Western blotting. IVIS Spectrum imaging and Laser Doppler Flow Metry are applied to explore the microcirculation hypoxia induced by NETs in the development of CIPN. Stroke Homing peptide (SHp)-guided deoxyribonuclease 1 (DNase1) is used to degrade NETs. Findings: The level of NETs in patients received chemotherapy increases significantly. And NETs accumulate in the DRG and limbs in CIPN mice. It leads to disturbed microcirculation and ischemic status in limbs and sciatic nerves treated with oxaliplatin (L-OHP). Furthermore, targeting NETs with DNase1 significantly reduces the chemotherapy-induced mechanical hyperalgesia. The pharmacological or genetic inhibition on myeloperoxidase (MPO) or peptidyl arginine deiminase-4 (PAD4) dramatically improves microcirculation disturbance caused by L-OHP and prevents the development of CIPN in mice. Interpretation: In addition to uncovering the role of NETs as a key element in the development of CIPN, our finding provides a potential therapeutic strategy that targeted degradation of NETs by SHp-guided DNase1 could be an effective treatment for CIPN. Funding: This study was funded by the National Natural Science Foundation of China 81870870, 81971047, 81773798, 82271252; Natural Science Foundation of Jiangsu Province BK20191253; Major Project of “Science and Technology Innovation Fund” of Nanjing Medical University 2017NJMUCX004; Key R&D Program (Social Development) Project of Jiangsu Province BE2019732; Nanjing Special Fund for Health Science and Technology Development YKK19170.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2352-3964
Relation: http://www.sciencedirect.com/science/article/pii/S2352396423000646; https://doaj.org/toc/2352-3964
DOI: 10.1016/j.ebiom.2023.104499
URL الوصول: https://doaj.org/article/f72ac0194d5840f7834d728dff91c84d
رقم الأكسشن: edsdoj.f72ac0194d5840f7834d728dff91c84d
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:23523964
DOI:10.1016/j.ebiom.2023.104499