Abstract:
Tubular epithelial cells (TCs) compose the majority of kidney parenchyma and play fundamental roles in maintaining homeostasis. Like other tissues, mostly immature TC with progenitor capabilities are able to replace TC lost during injury via clonal expansion and differentiation. In contrast, differentiated TC lack this capacity. However, as the kidney is frequently exposed to toxic injuries, evolution positively selected a response program that endows differentiated TC to maintain residual kidney function during kidney injury. Recently, we and others have described polyploidization of differentiated TC, a mechanism to augment the function of remnant TC after injury by rapid hypertrophy. Polyploidy is a condition characterized by >2 complete sets of chromosomes. Polyploid cells often display an increased functional capacity and are generally more resilient to stress as evidenced by being conserved across many plants and eukaryote species from flies to mammals. Here, we discuss the occurrence of TC polyploidy in different contexts and conditions and how this integrates into existing concepts of kidney cell responses to injury. Collectively, we aim at stimulating the acquisition of novel knowledge in the kidney field as well as accelerating the translation of this basic response mechanism to the clinical sphere.
摘要:
肾小管上皮细胞(TC)构成肾脏实质的大部分,在维持体内平衡中起着重要作用。像其他组织一样,大多数具有祖细胞能力的未成熟TC能够通过克隆扩增和分化来替代损伤期间丢失的TC。相比之下,差异化的TC缺乏这种能力。然而,因为肾脏经常受到毒性损伤,进化积极选择了一个反应程序,该程序赋予分化的TC在肾损伤期间维持残余的肾功能。最近,我们和其他人描述了分化的TC的多倍体化,一种通过快速肥大损伤后增强残余TC功能的机制。多倍体是特征在于多于两组完整染色体的病症。多倍体细胞通常表现出增加的功能能力,并且通常对胁迫更具弹性,这通过在从苍蝇到哺乳动物的许多植物和真核生物物种中保守而证明。这里,我们讨论了TC多倍体在不同环境和条件下的发生,以及如何将其整合到肾细胞对损伤的反应的现有概念中.总的来说,我们的目标是刺激肾脏领域新知识的获取,并加速这一基本反应机制向临床领域的转化。