A PPAR gamma-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesisopen access
- Authors
- Lee, Aram; Papangeli, Irinna; Park, Youngsook; Jeong, Ha-Neul; Choi, Jihea; Kang, Hyesoo; Jo, Ha-Neul; Kim, Jongmin; Chun, Hyung J.
- Issue Date
- May-2017
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- SCIENTIFIC REPORTS, v.7
- Journal Title
- SCIENTIFIC REPORTS
- Volume
- 7
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/8558
- DOI
- 10.1038/s41598-017-02852-4
- ISSN
- 2045-2322
- Abstract
- Activation of the endothelium by pro-inflammatory stimuli plays a key role in the pathogenesis of a multitude of vascular diseases. Angiogenesis is a crucial component of the vascular response associated with inflammatory signaling. The CD40/CD40 ligand dyad in endothelial cells (EC) has a central role in promoting vascular inflammatory response; however, the molecular mechanism underlying this component of inflammation and angiogenesis is not fully understood. Here we report a novel microRNA mediated suppression of endothelial CD40 expression. We found that CD40 is closely regulated by miR-424 and miR-503, which directly target its 3' untranslated region. Pro-inflammatory stimuli led to increased endothelial CD40 expression, at least in part due to decreased miR-424 and miR-503 expression. In addition, miR-424 and miR-503 reduced LPS induced EC sprouting, migration and tube formation. Moreover, we found that miR-424 and miR-503 expression is directly regulated by peroxisome proliferator-activated receptor gamma (PPAR gamma), whose endothelial expression and activity are decreased in response to inflammatory factors. Finally, we demonstrate that mice with endothelial-specific deletion of miR-322 (miR-424 ortholog) and miR-503 have augmented angiogenic response to LPS in a Matrigel plug assay. Overall, these studies identify a PPAR gamma-dependent miR-424/503-CD40 signaling axis that is critical for regulation of inflammation mediated angiogenesis.
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