標題: MicroRNA-483 amelioration of experimental pulmonary hypertension
作者: Zhang, Jin
He, Yangyang
Yan, Xiaosong
Chen, Shanshan
He, Ming
Lei, Yuyang
Zhang, Jiao
Gongol, Brendan
Gu, Mingxia
Miao, Yifei
Bai, Liang
Cui, Xiaopei
Wang, Xiaojian
Zhang, Yixin
Fan, Fenling
Li, Zhao
Shen, Yuan
Chou, Chih-Hung
Huang, Hsien-Da
Malhotra, Atul
Rabinovitch, Marlene
Jing, Zhi-Cheng
Shyy, John Y-J
生物科技學系
Department of Biological Science and Technology
關鍵字: miR-483;endothelium;pulmonary hypertension;TGF-beta
公開日期: 8-May-2020
摘要: Endothelial dysfunction is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH) and that exogenously administered microRNA may be of therapeutic benefit. Lower levels of miR-483 were found in serum from patients with idiopathic pulmonary arterial hypertension (IPAH), particularly those with more severe disease. RNA-seq and bioinformatics analyses showed that miR-483 targets several PAH-related genes, including transforming growth factor-beta (TGF-beta), TGF-beta receptor 2 (TGFBR2), beta-catenin, connective tissue growth factor (CTGF), interleukin-1 beta (IL-1 beta), and endothelin-1 (ET-1). Overexpression of miR-483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF-beta, TGFBR2, beta-catenin, CTGF, IL-1 beta, and ET-1. In contrast, inhibition of miR-483 increased these genes in ECs. Rats with EC-specific miR-483 overexpression exhibited ameliorated pulmonary hypertension (PH) and reduced right ventricular hypertrophy on challenge with monocrotaline (MCT) or Sugen + hypoxia. A reversal effect was observed in rats that received MCT with inhaled lentivirus overexpressing miR-483. These results indicate that PAH is associated with a reduced level of miR-483 and that miR-483 might reduce experimental PH by inhibition of multiple adverse responses.
URI: http://dx.doi.org/10.15252/emmm.201911303
http://hdl.handle.net/11536/154523
ISSN: 1757-4676
DOI: 10.15252/emmm.201911303
期刊: EMBO MOLECULAR MEDICINE
Volume: 12
Issue: 5
起始頁: 0
結束頁: 0
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