Poureetezadi Shahram Jevin, Wingert Rebecca A
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
Gen Med (Los Angel). 2013 Sep 1;1(3):112. doi: 10.4172/2327-5146.1000112.
Today, acute kidney injury (AKI) and congenital anomalies of the kidney and urinary tract (CAKUT) represent major issues in healthcare. Both AKI and CAKUT can lead to end stage renal disease (ESRD) that requires life-long medical care with renal replacement therapy. Renal replacement by dialysis is intensive, and kidney transplantation is restricted by organ availability. These limitations, along with the growing epidemic of patients affected by kidney disease, highlight the significant need to identify alternative ways to treat renal injury and birth defects. Drug discovery is one promising avenue of current research. Here, we discuss zebrafish chemical genetics and its latent potency as a method to rapidly identify small molecule therapeutics to accelerate recovery after AKI. Specifically, we review two groundbreaking studies that have recently provided a template to screen for compounds that expand the renal progenitor field in development that were capable of treating AKI in both the zebrafish and the mouse. These new findings demonstrate that drug discovery using zebrafish can be used for relevant translational research to identify clinical interventions for renal conditions in humans.
如今,急性肾损伤(AKI)和先天性肾脏和尿路异常(CAKUT)是医疗保健领域的重大问题。AKI和CAKUT都可能导致终末期肾病(ESRD),而这需要通过肾脏替代疗法进行终身医疗护理。透析进行的肾脏替代治疗强度大,而肾脏移植则受器官可用性的限制。这些限制,再加上受肾脏疾病影响的患者日益增多,凸显了寻找治疗肾损伤和出生缺陷替代方法的迫切需求。药物发现是当前研究中一个很有前景的途径。在此,我们讨论斑马鱼化学遗传学及其作为一种快速识别小分子疗法以加速AKI后恢复的方法的潜在效力。具体而言,我们回顾两项开创性研究,它们最近提供了一个筛选化合物的模板,这些化合物可在发育过程中扩大肾祖细胞领域,并且能够治疗斑马鱼和小鼠的AKI。这些新发现表明,利用斑马鱼进行药物发现可用于相关的转化研究,以确定针对人类肾脏疾病的临床干预措施。