Marrone April K, Ho Jacqueline
Division of Nephrology, Children's Hospital of Pittsburgh of UPMC, 4401 Penn Ave, Pittsburgh, PA, 15224, USA.
Pediatr Nephrol. 2014 Apr;29(4):565-74. doi: 10.1007/s00467-013-2599-0. Epub 2013 Sep 3.
Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of childhood chronic kidney disease (CKD). While mutations in several renal development genes have been identified as causes for CAKUT, most cases have not yet been linked to known mutations. Furthermore, the genotype-phenotype correlation is variable, suggesting that there might be additional factors that have an impact on the severity of CAKUT. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level, and are involved in many developmental processes. Although little is known about the function of specific miRNAs in kidney development, several have recently been shown to regulate the expression of, and/or are regulated by, crucial renal development genes present in other organ systems. In this review, we discuss how miRNA regulation of common developmental signaling pathways may be applicable to renal development. We focus on genes that are known to contribute to CAKUT in humans, for which miRNA interactions in other contexts have been identified, with miRNAs that are present in the kidney. We hypothesize that miRNA-mediated processes might play a role in kidney development through similar mechanisms, and speculate that genotypic variations in these small RNAs or their targets could be associated with CAKUT.
先天性肾脏和尿路畸形(CAKUT)是儿童慢性肾脏病(CKD)的主要病因。虽然已确定几种肾脏发育基因的突变是CAKUT的病因,但大多数病例尚未与已知突变相关联。此外,基因型与表型的相关性是可变的,这表明可能存在其他影响CAKUT严重程度的因素。微小RNA(miRNA)是一类小的非编码RNA,在转录后水平调节基因表达,并参与许多发育过程。虽然对特定miRNA在肾脏发育中的功能了解甚少,但最近有研究表明,几种miRNA可调节其他器官系统中关键肾脏发育基因的表达,和/或受这些基因调控。在本综述中,我们讨论了miRNA对常见发育信号通路的调控如何应用于肾脏发育。我们重点关注已知会导致人类CAKUT的基因,这些基因在其他情况下的miRNA相互作用已被确定,以及肾脏中存在的miRNA。我们假设miRNA介导的过程可能通过类似机制在肾脏发育中发挥作用,并推测这些小RNA或其靶标的基因型变异可能与CAKUT有关。