Departments of Pediatrics and Biology, Child Health Research Center, University of Virginia School of Medicine, Charlottesville, Virginia.
Circ Res. 2021 Apr 2;128(7):887-907. doi: 10.1161/CIRCRESAHA.121.318064. Epub 2021 Apr 1.
Renin cells are essential for survival perfected throughout evolution to ensure normal development and defend the organism against a variety of homeostatic threats. During embryonic and early postnatal life, they are progenitors that participate in the morphogenesis of the renal arterial tree. In adult life, they are capable of regenerating injured glomeruli, control blood pressure, fluid-electrolyte balance, tissue perfusion, and in turn, the delivery of oxygen and nutrients to cells. Throughout life, renin cell descendants retain the plasticity or memory to regain the renin phenotype when homeostasis is threatened. To perform all of these functions and maintain well-being, renin cells must regulate their identity and fate. Here, we review the major mechanisms that control the differentiation and fate of renin cells, the chromatin events that control the memory of the renin phenotype, and the major pathways that determine their plasticity. We also examine how chronic stimulation of renin cells alters their fate leading to the development of a severe and concentric hypertrophy of the intrarenal arteries and arterioles. Lastly, we provide examples of additional changes in renin cell fate that contribute to equally severe kidney disorders.
肾素细胞对于生存至关重要，它们在进化过程中不断完善，以确保正常的发育，并抵御各种体内平衡威胁。在胚胎期和出生后的早期，它们是祖细胞，参与肾动脉树的形态发生。在成年期，它们能够再生受损的肾小球，控制血压、液体电解质平衡、组织灌注，从而为细胞输送氧气和营养物质。在整个生命周期中，肾素细胞的后代保持着可塑性或记忆，以在体内平衡受到威胁时恢复肾素表型。为了执行所有这些功能并保持健康，肾素细胞必须调节其身份和命运。在这里，我们回顾了控制肾素细胞分化和命运的主要机制、控制肾素表型记忆的染色质事件，以及决定其可塑性的主要途径。我们还研究了慢性刺激肾素细胞如何改变它们的命运，导致肾内动脉和小动脉严重且同心性肥大的发展。最后，我们提供了肾素细胞命运发生其他变化的例子，这些变化同样导致严重的肾脏疾病。
