Department of Pediatrics, Division of Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Department of Pediatrics, Division of Medical Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Pediatr Nephrol. 2021 Nov;36(11):3539-3546. doi: 10.1007/s00467-020-04866-z. Epub 2021 Jan 7.
Acute kidney injury (AKI) is an extremely common medical affliction affecting both adult and pediatric patients resulting from hypoxic, nephrotoxic, and septic insults affecting approximately 20% of all hospital patients and up to 50% of patients in the intensive care unit. There are currently no therapeutics for patients who suffer AKI. Much recent work has focused on designing and implementing therapeutics for AKI. This review focuses on a family of enzymes known as sirtuins that play critical roles in regulating many cellular and biological functions. There are 7 mammalian sirtuins (SIRT1-7) that play roles in regulating the acylation of a wide variety of pathways. Furthermore, all but one of the mammalian sirtuins have been shown to play critical roles in mediating AKI based on preclinical studies. These diverse enzymes show exciting potential for therapeutic manipulation. This review will focus on the specific roles of each of the investigated sirtuins and the potential for manipulation of the various sirtuins and their effector pathways in mediating kidney injury.
急性肾损伤（AKI）是一种极其常见的医学疾病，影响成人和儿科患者，由缺氧、肾毒性和感染性损伤引起，约影响所有住院患者的 20%，多达 50%的重症监护病房患者。目前，对于患有 AKI 的患者，尚无治疗方法。最近的许多工作都集中在设计和实施 AKI 的治疗方法上。这篇综述重点介绍了一组称为沉默调节蛋白的酶，它们在调节许多细胞和生物学功能方面起着关键作用。哺乳动物中有 7 种沉默调节蛋白（SIRT1-7），它们在调节各种途径的酰化作用方面发挥作用。此外，除了一种哺乳动物沉默调节蛋白外，所有哺乳动物沉默调节蛋白都已被证明基于临床前研究在介导 AKI 中发挥关键作用。这些不同的酶在治疗干预方面显示出令人兴奋的潜力。这篇综述将重点介绍每个被研究的沉默调节蛋白的具体作用，以及操纵各种沉默调节蛋白及其效应途径在介导肾损伤方面的潜在作用。
