Departments of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Int J Mol Sci. 2018 Jun 12;19(6):1744. doi: 10.3390/ijms19061744.
Suboptimal early-life conditions affect the developing kidney, resulting in long-term programming effects, namely renal programming. Adverse renal programming increases the risk for developing hypertension and kidney disease in adulthood. Conversely, reprogramming is a strategy aimed at reversing the programming processes in early life. AMP-activated protein kinase (AMPK) plays a key role in normal renal physiology and the pathogenesis of hypertension and kidney disease. This review discusses the regulation of AMPK in the kidney and provides hypothetical mechanisms linking AMPK to renal programming. This will be followed by studies targeting AMPK activators like metformin, resveratrol, thiazolidinediones, and polyphenols as reprogramming strategies to prevent hypertension and kidney disease. Further studies that broaden our understanding of AMPK isoform- and tissue-specific effects on renal programming are needed to ultimately develop reprogramming strategies. Despite the fact that animal models have provided interesting results with regard to reprogramming strategies targeting AMPK signaling to protect against hypertension and kidney disease with developmental origins, these results await further clinical translation.
不良的早期生活条件会影响发育中的肾脏，导致长期的编程效应，即肾脏编程。不利的肾脏编程会增加成年后患高血压和肾脏疾病的风险。相反，重编程是一种旨在逆转早期生活中编程过程的策略。AMP 激活的蛋白激酶 (AMPK) 在正常肾脏生理学以及高血压和肾脏疾病的发病机制中起着关键作用。本综述讨论了 AMPK 在肾脏中的调节作用，并提供了将 AMPK 与肾脏编程联系起来的假设机制。接下来将讨论针对 AMPK 激活剂（如二甲双胍、白藜芦醇、噻唑烷二酮和多酚）的研究，这些激活剂作为重编程策略可预防高血压和肾脏疾病。需要进一步的研究来拓宽我们对 AMPK 同工型和组织特异性对肾脏编程的影响的理解，从而最终开发重编程策略。尽管动物模型在针对 AMPK 信号的重编程策略方面提供了有趣的结果，以预防具有发育起源的高血压和肾脏疾病，但这些结果仍有待进一步的临床转化。
