Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey.
Department of Medicine, Koc University School of Medicine, Istanbul, Turkey.
Nephrol Dial Transplant. 2024 Sep 27;39(10):1574-1582. doi: 10.1093/ndt/gfae066.
Intrauterine development is crucial for life-long health; therefore, elucidation of its key regulators is of interest for their potential prognostic and therapeutic implications. Originally described as a membrane-bound anti-aging protein, Klotho has evolved as a regulator of numerous functions in different organ systems. Circulating Klotho is generated by alternative splicing or active shedding from cell membranes. Recently, Klotho was identified as a regulator of placental function, and while Klotho does not cross the placental barrier, increased levels of circulating α-Klotho have been identified in umbilical cord blood compared with maternal blood, indicating that Klotho may also play a role in intrauterine development. In this narrative review, we discuss novel insights into the specific functions of the Klotho proteins in the placenta and in intrauterine development, while summarizing up-to-date knowledge about their structures and functions. Klotho plays a role in stem cell functioning, organogenesis and haematopoiesis. Low circulating maternal and foetal levels of Klotho are associated with preeclampsia, intrauterine growth restriction, and an increased perinatal risk for newborns, indicating a potential use of Klotho as biomarker and therapeutic target. Experimental administration of Klotho protein indicates a neuro- and nephroprotective potential, suggesting a possible future role of Klotho as a therapeutic agent. However, the use of Klotho as intervention during pregnancy is as yet unproven. Here, we summarize novel evidence, suggesting Klotho as a key regulator for healthy pregnancies and intrauterine development with promising potential for clinical use.
子宫内发育对终生健康至关重要；因此，阐明其关键调节因子对于其潜在的预后和治疗意义具有重要意义。Klotho 最初被描述为一种膜结合的抗衰老蛋白，现已演变为不同器官系统中众多功能的调节剂。循环 Klotho 是通过选择性剪接或从细胞膜上的活性脱落产生的。最近，Klotho 被鉴定为胎盘功能的调节剂，虽然 Klotho 不能穿过胎盘屏障，但在脐带血中与母血相比，循环α-Klotho 的水平升高，表明 Klotho 也可能在子宫内发育中发挥作用。在这篇叙述性综述中，我们讨论了 Klotho 蛋白在胎盘和子宫内发育中的特定功能的新见解，同时总结了它们的结构和功能的最新知识。Klotho 在干细胞功能、器官发生和造血中发挥作用。母体和胎儿循环中 Klotho 水平低与子痫前期、宫内生长受限以及新生儿围产期风险增加有关，表明 Klotho 可能作为生物标志物和治疗靶点具有潜在用途。Klotho 蛋白的实验给药表明具有神经和肾保护潜力，这表明 Klotho 将来可能作为一种治疗剂发挥作用。然而，Klotho 在怀孕期间的应用作为干预措施尚未得到证实。在这里，我们总结了新的证据，表明 Klotho 是健康妊娠和子宫内发育的关键调节因子，具有潜在的临床应用前景。
