红细胞ENT1-AMPD3轴是一个必不可少的纯能低氧传感器和能量调节器,在小鼠模型中对抗CKD
Changhan Chen1,2,3,4, TingTing Xie1,4,5, Yujin Zhang1
1National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Journal of the American Society of Nephrology : JASN
|September 19, 2023
概括
红细胞ENT1-AMPD3在缺氧期间调节能量,对抗慢性病 (CKD) 中的损伤. 这一途径为CKD进展提供了潜在的早期诊断和治疗点.
科学领域:
- 细胞代谢的细胞代谢.
- 脏生理学 脏生理学
- 低氧反应的反应
背景情况:
- 缺氧是损伤和慢性病 (CKD) 进展的关键驱动因素.
- 红细胞感知和响应CKD中缺氧的特定机制仍然不完全理解.
研究的目的:
- 调查红细胞平衡核酸转运体1 (ENT1) 和AMP脱氨酶3 (AMPD3) 在CKD中缺氧反应中的作用.
- 确定红细胞衍生的生物标志物和治疗瘤的治疗点.
主要方法:
- 产生红细胞特异性ENT1缺陷 (eEnt1-/-) 和全球AMPD3缺陷 (Ampd3-/-) 的小鼠.
- 使用了两个CKD模型:血管新素II输注和单边尿路阻塞 (UUO).
- 采用了代谢学,同位素流量分析,生物化学分析,遗传学研究和人类红细胞的转化研究.
主要成果:
- eEnt1-/-小鼠表现出严重的缺氧,损伤和纤维化,与受损的腺吸收和AMPK-BPGM激活有关.
- 失去eENT1导致谷氨减少,氧化应激增加,随后AMPD3激活,恶化缺氧.
- 缺乏AMPD3可保存红细胞能量,激活AMPK-BPGM,增强氧气输送,并提供抗氧化保护,减轻CKD的进展.
结论:
- 红细胞ENT1-AMPD3作为CKD中缺氧反应的关键调节者.
- 这一途径促进新陈代谢重编程,氧气输送和能量供应,从而对抗缺氧和CKD进展.
- ENT1-AMPD3-AMPK-BPGM轴代表了早期CKD诊断和治疗的有希望的目标.
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