ReviewThe Function of MicroRNAs in Renal Development and Pathophysiology
Introduction
MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs (21–25 nucleotides) that negatively regulate gene expression at the post-transcriptional level, predominantly by binding to the 3′-untranslated region (UTR) of target mRNAs through sequence pairing (Bartel, 2004; He and Hannon, 2004; Zhang and Su, 2009). Currently, more than 20,000 miRNAs from over 140 species are listed in miRBase version 19 (http://www.mirbase.org). It is now evident that miRNAs play an important role in a wide range of biological processes, including organ development (Tzur et al., 2009; Eda et al., 2011), cell differentiation (Nissan et al., 2011), apoptosis (Yu et al., 2010), tumorigenesis and metastasis (Liu and Chen, 2010; Ma et al., 2010; Zhao et al., 2012). Numerous computational approaches and databases have been developed to predict and annotate miRNA target genes (Rajewsky, 2006; Betel et al., 2008; Zhou et al., 2011), and notably quite a number of these targets are key regulators in various signaling pathways. Recently, the discovery of renal-specific and nephrosis-related miRNAs suggests that miRNAs may serve as significant modulators in kidney physiology and pathology. Considering that several comprehensive reviews of miRNA research on kidney have been previously published (Karolina et al., 2009; Liang et al., 2009; Saal and Harvey, 2009; Akkina and Becker, 2011; Bhatt et al., 2011; Chandrasekaran et al., 2012; Ho and Kreidberg, 2012), this review will focus on the current research progress of miRNA in renal development and discuss the major challenges for further study on kidney diseases.
Section snippets
Major stages of renal development
Kidney organogenesis is a complex process that requires the interplay of many cellular behaviors, including mesenchymal-to-epithelial transition, epithelial cell polarization and branching morphogenesis. These cellular alterations lead to the coordinated growth and differentiation of multiple highly specialized renal cell types (Dressler, 2006). The first genetic study on renal development was reported in 1956 (Grobstein, 1956). Since then, our knowledge of the gene expression patterns and
miRNAs in renal pathophysiology
Kidney is an important organ and it has four vital functions: (1) it serves as a natural filter of the blood and reabsorbs water, glucose, and amino acids from the filtrate; (2) it excretes wastes such as urea and ammonium; (3) it regulates the balance of electrolytes and acid–base; and (4) it produces hormones, including calcitriol, erythropoietin, and the enzyme rennin, which modulates blood pressure. Recent studies have proven that miRNAs play important roles in a variety of renal diseases,
Perspectives and challenges
Although Dicer or Drosha knockout models revealed that miRNAs are necessary for normal kidney development, the regulatory mechanisms of individual miRNAs during this multiple-stage process remain unclear. It is predicted that more miRNAs are important for the nephrogenic process besides miR-30 and miR-200, considering the highly complex structure of the kidney as well as the intricate regulatory networks that control its development and function, which encompass a large number of genes and
Acknowledgements
This work was supported by the National Natural Science Foundation of China (Nos. 81070589 and 31230042) and the National Basic Research Program of China (973 Program) (No. 2011CB811300).
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