An endothelial apelin-FGF link mediated by miR-424 and miR-503 is disrupted in pulmonary arterial hypertension
- Authors
- Kim, J (Kim, Jongmin); Kang, YJ (Kang, Yujung); Kojima, Y (Kojima, Yoko); Lighthouse, JK (Lighthouse, Ja; Hu, XY (Hu, Xiaoyue); Aldred, MA (Aldred, Micheala A; McLean, DL (McLean, Danielle L; Park, H (Park, Hyekyung); Comhair, SA (Comhair, Suzy A.); Greif, DM (Greif, Daniel M.); Erzurum, SC (Erzurum, Serpil C; Chun, HJ (Chun, Hyung J.)
- Issue Date
- Jan-2013
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- NATURE MEDICINE, v.19, no.1, pp 74 - 82
- Pages
- 9
- Journal Title
- NATURE MEDICINE
- Volume
- 19
- Number
- 1
- Start Page
- 74
- End Page
- 82
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/147505
- DOI
- 10.1038/nm.3040
- ISSN
- 1078-8956
1546-170X
- Abstract
- Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling associated with obliteration of pulmonary arterioles and formation of plexiform lesions composed of hyperproliferative endothelial and vascular smooth-muscle cells. Here we describe a microRNA (miRNA)-dependent association between apelin (APLN) and fibroblast growth factor 2 (FGF2) signaling in pulmonary artery endothelial cells (PAECs). APLN deficiency in these cells led to increased expression of FGF2 and its receptor FGFR1 as a consequence of decreased expression of miR-424 and miR-503, which directly target FGF2 and FGFR1. miR-424 and miR-503 were downregulated in PAH, exerted antiproliferative effects in PAECs and inhibited the capacity of PAEC-conditioned medium to induce the proliferation of pulmonary artery smooth-muscle cells. Reconstitution of miR-424 and miR-503 in vivo ameliorated pulmonary hypertension in experimental models. These studies identify an APLN-dependent miRNA-FGF signaling axis needed for the maintenance of pulmonary vascular homeostasis.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - 이과대학 > 생명시스템학부 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.