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The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis
- Title
- The atypical mechanosensitive microRNA-712 derived from pre-ribosomal RNA induces endothelial inflammation and atherosclerosis
- Authors
- Son, Dong Ju; Kumar, Sandeep; Takabe, Wakako; Kim, Chan Woo; Ni, Chih-Wen; Alberts-Grill, Noah; Jang, In-Hwan; Kim, Sangok; Kim, Wankyu; Kang, Sang Won; Baker, Andrew H.; Seo, Jai Woong; Ferrara, Katherine W.; Jo, Hanjoong
- Ewha Authors
- 강상원; 김완규
- SCOPUS Author ID
- 강상원; 김완규
- Issue Date
- 2013
- Journal Title
- NATURE COMMUNICATIONS
- ISSN
- 2041-1723
- Citation
- NATURE COMMUNICATIONS vol. 4
- Publisher
- NATURE PUBLISHING GROUP
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- MicroRNAs (miRNAs) regulate cardiovascular biology and disease, but the role of flow-sensitive microRNAs in atherosclerosis is still unclear. Here we identify miRNA-712 (miR-712) as a mechanosensitive miRNA upregulated by disturbed flow (d-flow) in endothelial cells, in vitro and in vivo. We also show that miR-712 is derived from an unexpected source, pre-ribosomal RNA, in an exoribonuclease-dependent but DiGeorge syndrome critical region 8 (DGCR8)-independent manner, suggesting that it is an atypical miRNA. Mechanistically, d-flow-induced miR-712 downregulates tissue inhibitor of metalloproteinase 3 (TIMP3) expression, which in turn activates the downstream matrix metalloproteinases (MMPs) and a disintegrin and metalloproteases (ADAMs) and stimulate pro-atherogenic responses, endothelial inflammation and permeability. Furthermore, silencing miR-712 by anti-miR-712 rescues TIMP3 expression and prevents atherosclerosis in murine models of atherosclerosis. Finally, we report that human miR-205 shares the same 'seed sequence' as murine-specific miR-712 and also targets TIMP3 in a flow-dependent manner. Targeting these mechanosensitive 'athero-miRs' may provide a new treatment paradigm in atherosclerosis.
- DOI
- 10.1038/ncomms4000
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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