Cirio M Cecilia, de Groh Eric D, de Caestecker Mark P, Davidson Alan J, Hukriede Neil A
Department of Developmental Biology, University of Pittsburgh, 3501 5th Ave., 5061 BST3, Pittsburgh, PA, 15213, USA.
Pediatr Nephrol. 2014 Apr;29(4):553-64. doi: 10.1007/s00467-013-2597-2. Epub 2013 Sep 5.
The vertebrate kidney has an inherent ability to regenerate following acute damage. Successful regeneration of the injured kidney requires the rapid replacement of damaged tubular epithelial cells and reconstitution of normal tubular function. Identifying the cells that participate in the regeneration process as well as the molecular mechanisms involved may reveal therapeutic targets for the treatment of kidney disease. Renal regeneration is associated with the expression of genetic pathways that are necessary for kidney organogenesis, suggesting that the regenerating tubular epithelium may be "reprogrammed" to a less-differentiated, progenitor state. This review will highlight data from various vertebrate models supporting the hypothesis that nephrogenic genes are reactivated as part of the process of kidney regeneration following acute kidney injury (AKI). Emphasis will be placed on the reactivation of developmental pathways and how our understanding of the resulting regeneration process may be enhanced by lessons learned in the embryonic kidney.
脊椎动物的肾脏在遭受急性损伤后具有内在的再生能力。受损肾脏的成功再生需要迅速替换受损的肾小管上皮细胞并重建正常的肾小管功能。确定参与再生过程的细胞以及其中涉及的分子机制,可能会揭示治疗肾脏疾病的靶点。肾脏再生与肾脏器官形成所必需的基因通路的表达有关,这表明再生的肾小管上皮可能会被“重新编程”为分化程度较低的祖细胞状态。本综述将重点介绍来自各种脊椎动物模型的数据,这些数据支持以下假设:在急性肾损伤(AKI)后,肾源性基因作为肾脏再生过程的一部分被重新激活。重点将放在发育通路的重新激活上,以及胚胎肾脏中获得的经验教训如何增进我们对由此产生的再生过程的理解。