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MicroRNA‐483 amelioration of experimental pulmonary hypertension
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), part...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207157/ https://www.ncbi.nlm.nih.gov/pubmed/32324970 http://dx.doi.org/10.15252/emmm.201911303 |
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author | 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 |
author_facet | 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 |
author_sort | Zhang, Jin |
collection | PubMed |
description | 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‐β (TGF‐β), TGF‐β receptor 2 (TGFBR2), β‐catenin, connective tissue growth factor (CTGF), interleukin‐1β (IL‐1β), and endothelin‐1 (ET‐1). Overexpression of miR‐483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF‐β, TGFBR2, β‐catenin, CTGF, IL‐1β, 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. |
format | Online Article Text |
id | pubmed-7207157 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72071572020-05-12 MicroRNA‐483 amelioration of experimental pulmonary hypertension 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 EMBO Mol Med Articles 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‐β (TGF‐β), TGF‐β receptor 2 (TGFBR2), β‐catenin, connective tissue growth factor (CTGF), interleukin‐1β (IL‐1β), and endothelin‐1 (ET‐1). Overexpression of miR‐483 in ECs inhibited inflammatory and fibrogenic responses, revealed by the decreased expression of TGF‐β, TGFBR2, β‐catenin, CTGF, IL‐1β, 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. John Wiley and Sons Inc. 2020-04-23 2020-05-08 /pmc/articles/PMC7207157/ /pubmed/32324970 http://dx.doi.org/10.15252/emmm.201911303 Text en © 2020 The Authors. Published under the terms of the CC BY 4.0 license This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles 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 MicroRNA‐483 amelioration of experimental pulmonary hypertension |
title | MicroRNA‐483 amelioration of experimental pulmonary hypertension |
title_full | MicroRNA‐483 amelioration of experimental pulmonary hypertension |
title_fullStr | MicroRNA‐483 amelioration of experimental pulmonary hypertension |
title_full_unstemmed | MicroRNA‐483 amelioration of experimental pulmonary hypertension |
title_short | MicroRNA‐483 amelioration of experimental pulmonary hypertension |
title_sort | microrna‐483 amelioration of experimental pulmonary hypertension |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7207157/ https://www.ncbi.nlm.nih.gov/pubmed/32324970 http://dx.doi.org/10.15252/emmm.201911303 |
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