Oxburgh Leif
The Rogosin Institute, New York, NY, United States.
Curr Top Dev Biol. 2022;148:237-263. doi: 10.1016/bs.ctdb.2021.12.007. Epub 2022 Feb 28.
The functional mass of kidney tissue in an adult is an important determinant of human health. Kidney formation during development is an essential determinant of the final nephron endowment of the adult organ, and no evidence has been reported that mice or humans are able to generate new nephrons after the developmental period. Mechanisms controlling organ growth after development are essential to establish the final adult organ size. The potential for organ growth is maintained in adult life and the size of one kidney may be significantly increased by loss of the contralateral kidney. The mouse has provided a model system for investigators to critically explore genetic, cell biological, and hormonal control of developmental and juvenile kidney growth. This article reviews three basic aspects of kidney size regulation: (1) Mechanisms that control nephron formation and how these are altered by the cessation of nephrogenesis at the end of the developmental period. (2) Applicability of the general model for growth hormone-insulin like growth factor control to kidney growth both pre- and postnatally. (3) Commonalities between mechanisms of juvenile kidney growth and the compensatory growth that is stimulated in adult life by reduction of kidney mass. Understanding the mechanisms that determine set-points for cell numbers and size in the kidney may inform ongoing efforts to generate kidney tissue from stem cells.
成体肾脏组织的功能质量是人类健康的重要决定因素。发育过程中的肾脏形成是成体器官最终肾单位数量的关键决定因素，目前尚无报道表明小鼠或人类在发育阶段后能够生成新的肾单位。控制发育后器官生长的机制对于确定成体器官的最终大小至关重要。成体生命中器官生长的潜能得以维持，对侧肾脏缺失可使一侧肾脏的大小显著增加。小鼠为研究人员提供了一个模型系统，用以深入探究发育和幼年肾脏生长的遗传、细胞生物学及激素调控。本文综述了肾脏大小调节的三个基本方面：（1）控制肾单位形成的机制，以及发育期末肾发生停止如何改变这些机制。（2）生长激素 - 胰岛素样生长因子控制的一般模型在产前和产后对肾脏生长的适用性。（3）幼年肾脏生长机制与成年期因肾脏质量减少而刺激的代偿性生长机制之间的共性。了解决定肾脏细胞数量和大小设定点的机制，可能为目前从干细胞生成肾脏组织的研究提供参考。
