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Silencing a disintegrin and metalloproteinase-33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling
Accumulating evidence suggests that pulmonary expression of a disintegrin and metalloproteinase-33 (ADAM33) serves a key role in the pathogenesis of airway remodeling-related diseases, including asthma. Airway vascular proliferation has been recognized as a key feature of airway remodeling. Our prev...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134872/ https://www.ncbi.nlm.nih.gov/pubmed/33982767 http://dx.doi.org/10.3892/mmr.2021.12141 |
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author | Yan, Fang Hao, Yanyan Gong, Xinji Sun, Hu Ding, Jianbing Wang, Jing |
author_facet | Yan, Fang Hao, Yanyan Gong, Xinji Sun, Hu Ding, Jianbing Wang, Jing |
author_sort | Yan, Fang |
collection | PubMed |
description | Accumulating evidence suggests that pulmonary expression of a disintegrin and metalloproteinase-33 (ADAM33) serves a key role in the pathogenesis of airway remodeling-related diseases, including asthma. Airway vascular proliferation has been recognized as a key feature of airway remodeling. Our previous study showed that ADAM33 is constitutively expressed in airway vascular smooth muscle cells in patients with asthma, suggesting a potential role of ADAM33 in regulating airway vascular remodeling. Using in vitro human aortic smooth muscle cells (HASMCs) and lentiviral vector carrying short hairpin RNA for ADAM33, the present study aimed to evaluate the influence of ADAM33 silencing on the proliferation and apoptosis of HASMCs and the underlying molecular pathways. Cellular proliferation was observed using the Cell Counting Kit-8 method. Cellular apoptosis was evaluated with Annexin V-PE/7-AAD staining and flow cytometry. Reverse transcription-quantitative PCR and western blotting were used to evaluate the changes in mRNA and protein levels of involved signaling molecules. It was found that silencing of ADAM33 expression in HASMCs significantly inhibited proliferation, but induced the apoptosis of HASMCs. These changes were accompanied by inhibition of the PI3K/AKT/ERK pathway and Bcl-2, but an increase in Bax expression. These results suggested that constitutive expression of ADAM33 may be important to maintain a proliferative phenotype in HASMCs. The influences of ADAM33 on proliferation and apoptosis of HASMCs may involve regulation of PI3K/AKT/ERK and Bax/Bcl-2 pathways. These findings suggested an important role of ADAM33 in airway vascular remodeling and potential therapeutic significance of ADAM33 inhibition in airway remodeling-related diseases. |
format | Online Article Text |
id | pubmed-8134872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-81348722021-05-24 Silencing a disintegrin and metalloproteinase-33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling Yan, Fang Hao, Yanyan Gong, Xinji Sun, Hu Ding, Jianbing Wang, Jing Mol Med Rep Articles Accumulating evidence suggests that pulmonary expression of a disintegrin and metalloproteinase-33 (ADAM33) serves a key role in the pathogenesis of airway remodeling-related diseases, including asthma. Airway vascular proliferation has been recognized as a key feature of airway remodeling. Our previous study showed that ADAM33 is constitutively expressed in airway vascular smooth muscle cells in patients with asthma, suggesting a potential role of ADAM33 in regulating airway vascular remodeling. Using in vitro human aortic smooth muscle cells (HASMCs) and lentiviral vector carrying short hairpin RNA for ADAM33, the present study aimed to evaluate the influence of ADAM33 silencing on the proliferation and apoptosis of HASMCs and the underlying molecular pathways. Cellular proliferation was observed using the Cell Counting Kit-8 method. Cellular apoptosis was evaluated with Annexin V-PE/7-AAD staining and flow cytometry. Reverse transcription-quantitative PCR and western blotting were used to evaluate the changes in mRNA and protein levels of involved signaling molecules. It was found that silencing of ADAM33 expression in HASMCs significantly inhibited proliferation, but induced the apoptosis of HASMCs. These changes were accompanied by inhibition of the PI3K/AKT/ERK pathway and Bcl-2, but an increase in Bax expression. These results suggested that constitutive expression of ADAM33 may be important to maintain a proliferative phenotype in HASMCs. The influences of ADAM33 on proliferation and apoptosis of HASMCs may involve regulation of PI3K/AKT/ERK and Bax/Bcl-2 pathways. These findings suggested an important role of ADAM33 in airway vascular remodeling and potential therapeutic significance of ADAM33 inhibition in airway remodeling-related diseases. D.A. Spandidos 2021-07 2021-05-09 /pmc/articles/PMC8134872/ /pubmed/33982767 http://dx.doi.org/10.3892/mmr.2021.12141 Text en Copyright: © Yan 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 Yan, Fang Hao, Yanyan Gong, Xinji Sun, Hu Ding, Jianbing Wang, Jing Silencing a disintegrin and metalloproteinase-33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling |
title | Silencing a disintegrin and metalloproteinase-33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling |
title_full | Silencing a disintegrin and metalloproteinase-33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling |
title_fullStr | Silencing a disintegrin and metalloproteinase-33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling |
title_full_unstemmed | Silencing a disintegrin and metalloproteinase-33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling |
title_short | Silencing a disintegrin and metalloproteinase-33 attenuates the proliferation of vascular smooth muscle cells via PI3K/AKT pathway: Implications in the pathogenesis of airway vascular remodeling |
title_sort | silencing a disintegrin and metalloproteinase-33 attenuates the proliferation of vascular smooth muscle cells via pi3k/akt pathway: implications in the pathogenesis of airway vascular remodeling |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134872/ https://www.ncbi.nlm.nih.gov/pubmed/33982767 http://dx.doi.org/10.3892/mmr.2021.12141 |
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