Department of Biological Sciences, Sookmyung Women's University, Seoul, South Korea.
Research Institute of Women's Health, Sookmyung Women's University, Seoul, South Korea.
FASEB J. 2019 Feb;33(2):2870-2884. doi: 10.1096/fj.201800563RR. Epub 2018 Oct 17.
Altered miRNA (miR) expression occurs in various diseases. However, the therapeutic effect of miRNAs in autosomal dominant polycystic kidney disease (ADPKD) is unclear. Genome-wide analyses of miRNA expression and DNA methylation status were conducted to identify crucial miRNAs in end-stage ADPKD. miR-192 and -194 levels were down-regulated with hypermethylation at these loci, mainly in the intermediate and late stages, not in the early stage, of cystogenesis, suggesting their potential impact on cyst expansion. Cyst expansion has been strongly associated with endothelial-mesenchymal transition (EMT). Zinc finger E-box-binding homeobox-2 and cadherin-2, which are involved in EMT, were directly regulated by miR-192 and -194. The therapeutic effect of miR-192 and -194 in vivo and in vitro were assessed. Restoring these miRs by injection of precursors influenced the reduced size of cysts in Pkd1 conditional knockout mice. miR-192 and -194 may act as potential therapeutic targets to control the expansion and progression of cysts in patients with ADPKD.-Kim, D. Y., Woo, Y. M., Lee, S., Oh, S., Shin, Y., Shin, J.-O., Park, E. Y., Ko, J. Y., Lee, E. J., Bok, J., Yoo, K. H., Park, J. H. Impact of miR-192 and miR-194 on cyst enlargement through EMT in autosomal dominant polycystic kidney disease.
miRNA（miR）表达的改变发生在各种疾病中。然而，miRNAs 在常染色体显性多囊肾病（ADPKD）中的治疗效果尚不清楚。对 miRNA 表达和 DNA 甲基化状态进行全基因组分析，以确定终末期 ADPKD 中的关键 miRNA。miR-192 和 -194 的水平下调与这些基因座的高甲基化有关，主要发生在囊泡形成的中晚期，而不是早期，表明它们对囊泡扩张有潜在影响。囊泡扩张与内皮-间充质转化（EMT）密切相关。锌指 E 盒结合同源盒 2 和钙黏蛋白-2，参与 EMT，直接受 miR-192 和 -194 调控。在体内和体外评估了 miR-192 和 -194 的治疗效果。通过注射前体恢复这些 miR 会影响 Pkd1 条件性敲除小鼠中囊肿体积的缩小。miR-192 和 -194 可能作为潜在的治疗靶点，以控制 ADPKD 患者囊肿的扩张和进展。-Kim, D. Y., Woo, Y. M., Lee, S., Oh, S., Shin, Y., Shin, J.-O., Park, E. Y., Ko, J. Y., Lee, E. J., Bok, J., Yoo, K. H., Park, J. H. 通过 EMT 在常染色体显性多囊肾病中影响囊肿增大的 miR-192 和 miR-194。
