在从AKI过渡到CKD期间,ATGL通过重新编程脂质代谢来调节纤维化
Xiaofan Li1, Jianwen Chen2, Jun Li3
1Department of Nephrology, First Medical Center of Chinese PLA General Hospital, National Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases Research, Beijing 100853, China; Chinese PLA Medical School, Beijing 100853, China.
概括
脂肪三糖 lipase (ATGL) 的下调会通过破坏脂肪酸氧化,使纤维化恶化. 恢复ATGL水平可以通过改善细胞中的脂质代谢来预防纤维化.
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
- 代谢疾病 代谢疾病
背景情况:
- 急性损伤 (AKI) 可以发展为慢性病 (CKD),导致纤维化.
- 管状上皮细胞 (TEC) 的修复受损是纤维化的主要驱动因素.
- 恢复脂肪酸β-氧化 (FAO) 显示出降低纤维化的潜力.
研究的目的:
- 调查脂肪甘油三酸脂酶 (ATGL) 在从AKI过渡到CKD以及随后的纤维化中的作用.
- 确定调节ATGL活性对脂代谢,线粒体功能和脏TEC中氧化应激的影响.
主要方法:
- 使用一只老鼠模型的AKI-CKD过渡.
- 服用ATGL抑制剂 (atglistatin) 并在体外和体内使用ATGL过度表达.
- 在TEC中评估了脂质积累,FAO水平,线粒体功能,氧化应激和亡.
主要成果:
- 在AKI-CKD过渡期间,ATGL在脏TEC中被发现是下调的.
- 抑制ATGL加剧了脂质积累,减少了FAO和线粒体功能,增加了氧化应激和亡,加剧了纤维化.
- 过度表达ATGL可以改善这些影响,抑制脂质积累,改善细胞功能,从而减少纤维化.
结论:
- 在调节纤维化方面,ATGL通过重编程脏TEC中的脂质代谢,起到关键作用.
- 向ATGL为治疗慢性病和预防纤维化提供了一个新的治疗策略.
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