Chu Andrew S, Friedman Joshua R
Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
J Clin Invest. 2008 Nov;118(11):3585-7. doi: 10.1172/JCI36870. Epub 2008 Oct 23.
The polycystic liver and kidney diseases are a family of disorders with heterogeneous etiologies. Proposed mechanisms of disease include ciliary dysfunction, excess cell proliferation, and altered cell-cell or cell-matrix interactions. In this issue of the JCI, Lee and colleagues provide data to support a novel mechanism for cystogenesis involving microRNA (miRNA) (see the related article beginning on page 3714). They demonstrate that levels of the miRNA miR15a are decreased in livers of patients with autosomal recessive and autosomal dominant polycystic kidney disease (ARPKD and ADPKD, respectively) and congenital hepatic fibrosis as well as in the PKC rat model of ARPKD. This results in increased expression of the cell-cycle regulator Cdc25A, which is a direct target of miR15a, and increased cellular proliferation and cystogenesis in vitro. These findings suggest that other miRNAs may also participate in the molecular pathogenesis of cystic liver and kidney diseases.
多囊肝和多囊肾疾病是一类病因各异的病症。提出的疾病机制包括纤毛功能障碍、细胞过度增殖以及细胞间或细胞与基质相互作用的改变。在本期《临床研究杂志》中，李及其同事提供数据支持了一种涉及微小RNA（miRNA）的新型囊肿形成机制（见第3714页开始的相关文章）。他们证明，在常染色体隐性和常染色体显性多囊肾病（分别为ARPKD和ADPKD）以及先天性肝纤维化患者的肝脏中，以及在ARPKD的PKC大鼠模型中，miRNA miR15a的水平降低。这导致细胞周期调节因子Cdc25A的表达增加，Cdc25A是miR15a的直接靶点，并在体外增加细胞增殖和囊肿形成。这些发现表明，其他miRNA也可能参与多囊肝和多囊肾疾病的分子发病机制。
