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Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice

Pulmonary hypertension (PH) remains a life-limiting disease characterized by pulmonary vascular remodelling due to aberrant proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), thus leading to raised pulmonary arterial pressure and right ventricular hypertrophy. Secreted gly...

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Autores principales: Zhang, Wei, Wang, Wang, Liu, Jie, Li, Jinna, Wang, Juan, Zhang, Yunxia, Zhang, Zhifei, Liu, Yafei, Jin, Yankun, Li, Jifeng, Cao, Jie, Wang, Chen, Ning, Wen, Wang, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374469/
https://www.ncbi.nlm.nih.gov/pubmed/28361925
http://dx.doi.org/10.1038/srep45820
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author Zhang, Wei
Wang, Wang
Liu, Jie
Li, Jinna
Wang, Juan
Zhang, Yunxia
Zhang, Zhifei
Liu, Yafei
Jin, Yankun
Li, Jifeng
Cao, Jie
Wang, Chen
Ning, Wen
Wang, Jun
author_facet Zhang, Wei
Wang, Wang
Liu, Jie
Li, Jinna
Wang, Juan
Zhang, Yunxia
Zhang, Zhifei
Liu, Yafei
Jin, Yankun
Li, Jifeng
Cao, Jie
Wang, Chen
Ning, Wen
Wang, Jun
author_sort Zhang, Wei
collection PubMed
description Pulmonary hypertension (PH) remains a life-limiting disease characterized by pulmonary vascular remodelling due to aberrant proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), thus leading to raised pulmonary arterial pressure and right ventricular hypertrophy. Secreted glycoprotein follistatin-like 1 (FSTL1) has been reported to ameliorate tissue remodelling in cardiovascular injuries. However, the role of FSTL1 in deranged pulmonary arteries remains elusive. We found that there were higher serum levels of FSTL1 in patients with PH related to chronic obstructive pulmonary diseases (COPD) and in mice model of hypoxia-induced PH (HPH). Haploinsufficiency of Fstl1 in mice contributed to an exacerbated HPH, as demonstrated by increased right ventricular systolic pressure, pulmonary arterial muscularization and right ventricular hypertrophy index. Conversely, FSTL1 administration attenuated HPH. In cultured human PASMCs, hypoxia-promoted cellular viability, DNA synthesis and migration were suppressed by exogenous FSTL1 but enhanced by small interfering RNA targeting FSTL1. Additionally, FSTL1 inhibited the proliferation and migration of PASMCs via extracellular regulated kinase (ERK) signal pathway. All these findings indicate that FSTL1 imposed a protective modulation on pulmonary vascular remodelling, thereby suggesting its role in the regulation of HPH.
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spelling pubmed-53744692017-04-03 Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice Zhang, Wei Wang, Wang Liu, Jie Li, Jinna Wang, Juan Zhang, Yunxia Zhang, Zhifei Liu, Yafei Jin, Yankun Li, Jifeng Cao, Jie Wang, Chen Ning, Wen Wang, Jun Sci Rep Article Pulmonary hypertension (PH) remains a life-limiting disease characterized by pulmonary vascular remodelling due to aberrant proliferation and migration of pulmonary artery smooth muscle cells (PASMCs), thus leading to raised pulmonary arterial pressure and right ventricular hypertrophy. Secreted glycoprotein follistatin-like 1 (FSTL1) has been reported to ameliorate tissue remodelling in cardiovascular injuries. However, the role of FSTL1 in deranged pulmonary arteries remains elusive. We found that there were higher serum levels of FSTL1 in patients with PH related to chronic obstructive pulmonary diseases (COPD) and in mice model of hypoxia-induced PH (HPH). Haploinsufficiency of Fstl1 in mice contributed to an exacerbated HPH, as demonstrated by increased right ventricular systolic pressure, pulmonary arterial muscularization and right ventricular hypertrophy index. Conversely, FSTL1 administration attenuated HPH. In cultured human PASMCs, hypoxia-promoted cellular viability, DNA synthesis and migration were suppressed by exogenous FSTL1 but enhanced by small interfering RNA targeting FSTL1. Additionally, FSTL1 inhibited the proliferation and migration of PASMCs via extracellular regulated kinase (ERK) signal pathway. All these findings indicate that FSTL1 imposed a protective modulation on pulmonary vascular remodelling, thereby suggesting its role in the regulation of HPH. Nature Publishing Group 2017-03-31 /pmc/articles/PMC5374469/ /pubmed/28361925 http://dx.doi.org/10.1038/srep45820 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Zhang, Wei
Wang, Wang
Liu, Jie
Li, Jinna
Wang, Juan
Zhang, Yunxia
Zhang, Zhifei
Liu, Yafei
Jin, Yankun
Li, Jifeng
Cao, Jie
Wang, Chen
Ning, Wen
Wang, Jun
Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice
title Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice
title_full Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice
title_fullStr Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice
title_full_unstemmed Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice
title_short Follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice
title_sort follistatin-like 1 protects against hypoxia-induced pulmonary hypertension in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5374469/
https://www.ncbi.nlm.nih.gov/pubmed/28361925
http://dx.doi.org/10.1038/srep45820
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