胎儿对营养过剩信号的重编程,O-GlcNAcylation,以及CKD的演变
1Baylor Heart and Vascular Institute , Dallas , Texas and Imperial College , London , United Kingdom.
Journal of the American Society of Nephrology : JASN
|June 21, 2023
概括
慢性病 (CKD) 涉及恢复胎儿脏编程,增加葡萄糖吸收和O-GlcNAcylation. 这种胎儿重编程与脏损伤有关,并表明CKD的治疗点.
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
- 代谢调节 代谢调节 代谢调节
背景情况:
- 胎儿脏发育依赖于低氧,低工作量环境中的糖解,mTOR和HIF-1α.
- 成年脏利用脂肪酸氧化 ATP 在一个 normoxic,高工作负载状态,由 sirtuin-1 和 AMPK 调节.
- 损伤会触发转移到胎儿信号程序,如果在高氧和工作量下持续下去,这是不适应的.
研究的目的:
- 研究胎儿重编程和O-GlcNAcylation在糖尿病和非糖尿病慢性病 (CKD) 的发展中的作用.
- 探索增强O-GlcNAcylation对细胞功能和疾病途径的影响.
- 检查脏保护性药物作用与中的O-GlcNAcylation水平之间的关联.
主要方法:
- 在胎儿和成人脏状态下对代谢和信号通路 (mTOR,HIF-1α,O-GlcNAcylation) 的分析.
- 在成年模型中对O-GlcNAcylation进行实验增强和变音.
- 在CKD患者和模型中对O-GlcNAcylation的临床和实验评估.
- 评估脏保护药物对脏O-GlcNAcylation的影响.
主要成果:
- 糖尿病和非糖尿病的CKD显示胎儿重编程与高调的mTOR和HIF-1α,以及增加的O-GlcNAcylation.
- 成人脏中增强的O-GlcNAcylation促进氧化应激,亡,炎症和纤维化,同时抑制了白蛋白内细胞分裂.
- 脏保护药物 (ARB,MRA,SGLT2抑制剂) 与脏O-GlcNAcylation降低有关,尽管因果关系尚未探索.
结论:
- 尿素二酸N-乙葡萄糖胺作为营养传感器,通过上调的mTOR和HIF-1α信号驱动CKD的发展.
- 持续的胎儿重编程和增加的O-GlcNAcylation是CKD发病的关键因素.
- 向O-GlcNAcylation通路可能为治疗CKD提供新的治疗策略.
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