Tweak/Fn14系统参与了拉布多米解引起的急性损伤
Melania Guerrero-Hue1, Mercedes Vallejo-Mudarra1, Cristina García-Caballero1
1Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Hospital Universitario Reina Sofía, Cordoba, Spain.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
|November 26, 2023
概括
这种TWEAK/Fn14通路在狂犬病溶解中驱动损伤,导致急性损伤和慢性病. 阻断这种通路为拉布多解诱导的损伤提供了潜在的治疗方法.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學專業.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 轮骨髓溶解是一种与急性损伤 (AKI) 和慢性病 (CKD) 相关的严重疾病.
- 已知TWEAK/Fn14信号通路会影响脏炎症和管状细胞死亡.
- TWEAK/Fn14在拉布多解诱导的损伤中的特定作用以前没有被描述.
研究的目的:
- 为了研究TWEAK/Fn14信号轴在与拉布多结合相关的损伤的发病过程中的功能作用.
- 为了探索阻断TWEAK/Fn14通路在狂犬病溶解中的治疗潜力.
主要方法:
- 在小鼠中诱导了体溶解,评估包括损伤,炎症,纤维化和细胞死亡.
- 研究涉及野生型,TWEAK和Fn14缺乏的小鼠,以及用TWEAK阻断抗体治疗的小鼠.
- 进行了体内和体外实验以阐明Fn14调节途径.
主要成果:
- 脏Fn14的表达增加与拉布多米解,与功能下降相关.
- 肌球蛋白通过ERK和p38途径诱导Fn14表达,而Nrf2激活则抑制了这种上调.
- 遗传性枯竭或阻断TWEAK/Fn14可以改善脏损伤,炎症和纤维化.
结论:
- TWEAK/Fn14轴与拉布地质溶解-AKI的发展和发展为AKI-CKD有关.
- 准TWEAK/Fn14通路是一个有前途的治疗策略,用于减轻在狂犬病发作中的损伤.
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