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Deficiency of filamin A in smooth muscle cells protects against hypoxia-mediated pulmonary hypertension in mice
Filamin A (FLNA) is a high molecular weight cytoskeleton protein important for cell locomotion. A relationship between FLNA mutations and pulmonary arterial hypertension (PAH) has previously been reported; however, the detailed mechanism remains unclear. The present study aimed to explore the role o...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911089/ https://www.ncbi.nlm.nih.gov/pubmed/36704846 http://dx.doi.org/10.3892/ijmm.2023.5225 |
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author | Zheng, Yaguo Ma, Hong Yan, Yufeng Ye, Peng Yu, Wande Lin, Song Chen, Shao-Liang |
author_facet | Zheng, Yaguo Ma, Hong Yan, Yufeng Ye, Peng Yu, Wande Lin, Song Chen, Shao-Liang |
author_sort | Zheng, Yaguo |
collection | PubMed |
description | Filamin A (FLNA) is a high molecular weight cytoskeleton protein important for cell locomotion. A relationship between FLNA mutations and pulmonary arterial hypertension (PAH) has previously been reported; however, the detailed mechanism remains unclear. The present study aimed to explore the role of FLNA in vascular smooth muscle cells during the development of PAH. Smooth muscle cell (SMC)-specific FLNA-deficient mice were generated and the mice were then exposed to hypoxia for 28 days to build the mouse model of PAH. Human pulmonary arterial smooth muscle cells (PASMCs) were also cultured and transfected with FLNA small interfering RNA or overexpression plasmids to investigate the effects of FLNA on PASMC proliferation and migration. Notably, compared with control individuals, the expression levels of FLNA were increased in lung tissues from patients with PAH, and it was obviously expressed in the PASMCs of pulmonary arterioles. FLNA deficiency in SMCs attenuated hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. In vitro studies suggested that absence of FLNA impaired PASMC proliferation and migration, and produced lower levels of phosphorylated (p)-PAK-1 and RAC1 activity. However, FLNA overexpression promoted PASMC proliferation and migration, and increased the expression levels of p-PAK-1 and RAC1 activity. The present study highlights the role of FLNA in pulmonary vascular remodeling; therefore, it could serve as a potential target for the treatment of PAH. |
format | Online Article Text |
id | pubmed-9911089 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-99110892023-02-10 Deficiency of filamin A in smooth muscle cells protects against hypoxia-mediated pulmonary hypertension in mice Zheng, Yaguo Ma, Hong Yan, Yufeng Ye, Peng Yu, Wande Lin, Song Chen, Shao-Liang Int J Mol Med Articles Filamin A (FLNA) is a high molecular weight cytoskeleton protein important for cell locomotion. A relationship between FLNA mutations and pulmonary arterial hypertension (PAH) has previously been reported; however, the detailed mechanism remains unclear. The present study aimed to explore the role of FLNA in vascular smooth muscle cells during the development of PAH. Smooth muscle cell (SMC)-specific FLNA-deficient mice were generated and the mice were then exposed to hypoxia for 28 days to build the mouse model of PAH. Human pulmonary arterial smooth muscle cells (PASMCs) were also cultured and transfected with FLNA small interfering RNA or overexpression plasmids to investigate the effects of FLNA on PASMC proliferation and migration. Notably, compared with control individuals, the expression levels of FLNA were increased in lung tissues from patients with PAH, and it was obviously expressed in the PASMCs of pulmonary arterioles. FLNA deficiency in SMCs attenuated hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. In vitro studies suggested that absence of FLNA impaired PASMC proliferation and migration, and produced lower levels of phosphorylated (p)-PAK-1 and RAC1 activity. However, FLNA overexpression promoted PASMC proliferation and migration, and increased the expression levels of p-PAK-1 and RAC1 activity. The present study highlights the role of FLNA in pulmonary vascular remodeling; therefore, it could serve as a potential target for the treatment of PAH. D.A. Spandidos 2023-01-26 /pmc/articles/PMC9911089/ /pubmed/36704846 http://dx.doi.org/10.3892/ijmm.2023.5225 Text en Copyright: © Zheng et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Zheng, Yaguo Ma, Hong Yan, Yufeng Ye, Peng Yu, Wande Lin, Song Chen, Shao-Liang Deficiency of filamin A in smooth muscle cells protects against hypoxia-mediated pulmonary hypertension in mice |
title | Deficiency of filamin A in smooth muscle cells protects against hypoxia-mediated pulmonary hypertension in mice |
title_full | Deficiency of filamin A in smooth muscle cells protects against hypoxia-mediated pulmonary hypertension in mice |
title_fullStr | Deficiency of filamin A in smooth muscle cells protects against hypoxia-mediated pulmonary hypertension in mice |
title_full_unstemmed | Deficiency of filamin A in smooth muscle cells protects against hypoxia-mediated pulmonary hypertension in mice |
title_short | Deficiency of filamin A in smooth muscle cells protects against hypoxia-mediated pulmonary hypertension in mice |
title_sort | deficiency of filamin a in smooth muscle cells protects against hypoxia-mediated pulmonary hypertension in mice |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9911089/ https://www.ncbi.nlm.nih.gov/pubmed/36704846 http://dx.doi.org/10.3892/ijmm.2023.5225 |
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