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Impact of miR-192 and miR-194 on Cyst Enlargement Through EMT in Autosomal Dominant Polycystic Kidney Disease

 Do Yeon Kim  ;  Yu Mi Woo  ;  Sunyoung Lee  ;  Sumin Oh  ;  Yubin Shin  ;  Jeong-Oh Shin  ;  Eun Young Park  ;  Je Yeong Ko  ;  Eun Ji Lee  ;  Jinwoong Bok  ;  Kyung Hyun Yoo  ;  Jong Hoon Park 
 FASEB JOURNAL, Vol.33(2) : 2870-2884, 2019-02 
Journal Title
Issue Date
Animals ; Antigens, CD / genetics ; Antigens, CD / metabolism ; Cadherins / genetics ; Cadherins / metabolism ; Case-Control Studies ; DNA Methylation ; Disease Models, Animal ; Epithelial-Mesenchymal Transition* ; Gene Expression Profiling ; Gene Expression Regulation* ; Genome-Wide Association Study ; Humans ; Mice ; Mice, Knockout ; MicroRNAs / genetics* ; Polycystic Kidney, Autosomal Dominant / genetics ; Polycystic Kidney, Autosomal Dominant / metabolism ; Polycystic Kidney, Autosomal Dominant / pathology* ; Protein-Serine-Threonine Kinases / physiology* ; Pyruvate Dehydrogenase (Acetyl-Transferring) Kinase ; Zinc Finger E-box Binding Homeobox 2 / genetics ; Zinc Finger E-box Binding Homeobox 2 / metabolism
ADPKD ; DNA methylation ; N-cadherin ; ZEB2 ; microRNA
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.
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1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
Shin, Jeong Oh(신정오) ORCID logo https://orcid.org/0000-0002-6935-0936
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