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Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension
Pulmonary hypertension (PH) is a chronic vascular proliferative disorder. While cigarette smoke (CS) plays a vital part in PH related to chronic obstructive pulmonary disease (COPD). Methyl-CpG-Binding Domain Protein 2 (MBD2) has been linked to multiple proliferative diseases. However, the specific...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243313/ https://www.ncbi.nlm.nih.gov/pubmed/35785161 http://dx.doi.org/10.3389/fonc.2022.879793 |
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author | Wu, Jixing Huang, Qian Li, Qinghai Gu, Yiya Zhan, Yuan Wang, Ting Chen, Jinkun Zeng, Zhilin Lv, Yongman Zhao, Jianping Xia, Jie Xie, Jungang |
author_facet | Wu, Jixing Huang, Qian Li, Qinghai Gu, Yiya Zhan, Yuan Wang, Ting Chen, Jinkun Zeng, Zhilin Lv, Yongman Zhao, Jianping Xia, Jie Xie, Jungang |
author_sort | Wu, Jixing |
collection | PubMed |
description | Pulmonary hypertension (PH) is a chronic vascular proliferative disorder. While cigarette smoke (CS) plays a vital part in PH related to chronic obstructive pulmonary disease (COPD). Methyl-CpG-Binding Domain Protein 2 (MBD2) has been linked to multiple proliferative diseases. However, the specific mechanisms of MBD2 in CS-induced PH remain to be elucidated. Herein, the differential expression of MBD2 was tested between the controls and the PH patients’ pulmonary arteries, CS-exposed rat models’ pulmonary arteries, and primary human pulmonary artery smooth muscle cells (HPASMCs) following cigarette smoke extract (CSE) stimulation. As a result, PH patients and CS-induced rats and HPASMCs showed an increase in MBD2 protein expression compared with the controls. Then, MBD2 silencing was used to investigate the function of MBD2 on CSE-induced HPASMCs’ proliferation, migration, and cell cycle progression. As a consequence, CSE could induce HPASMCs’ increased proliferation and migration, and cell cycle transition, which were suppressed by MBD2 interference. Furthermore, RNA-seq, ChIP-qPCR, and MassARRAY were conducted to find out the downstream mechanisms of MBD2 for CS-induced pulmonary vascular remodeling. Subsequently, RNA-seq revealed MBD2 might affect the transcription of BMP2 gene, which furtherly altered the expression of BMP2 protein. ChIP-qPCR demonstrated MBD2 could bind BMP2’s promotor. MassARRAY indicated that MBD2 itself could not directly affect DNA methylation. In sum, our results indicate that increased MBD2 expression promotes CS-induced pulmonary vascular remodeling. The fundamental mechanisms may be that MBD2 can bind BMP2’s promoter and downregulate its expression. Thus, MBD2 may promote the occurrence of the CS-induced PH. |
format | Online Article Text |
id | pubmed-9243313 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92433132022-07-01 Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension Wu, Jixing Huang, Qian Li, Qinghai Gu, Yiya Zhan, Yuan Wang, Ting Chen, Jinkun Zeng, Zhilin Lv, Yongman Zhao, Jianping Xia, Jie Xie, Jungang Front Oncol Oncology Pulmonary hypertension (PH) is a chronic vascular proliferative disorder. While cigarette smoke (CS) plays a vital part in PH related to chronic obstructive pulmonary disease (COPD). Methyl-CpG-Binding Domain Protein 2 (MBD2) has been linked to multiple proliferative diseases. However, the specific mechanisms of MBD2 in CS-induced PH remain to be elucidated. Herein, the differential expression of MBD2 was tested between the controls and the PH patients’ pulmonary arteries, CS-exposed rat models’ pulmonary arteries, and primary human pulmonary artery smooth muscle cells (HPASMCs) following cigarette smoke extract (CSE) stimulation. As a result, PH patients and CS-induced rats and HPASMCs showed an increase in MBD2 protein expression compared with the controls. Then, MBD2 silencing was used to investigate the function of MBD2 on CSE-induced HPASMCs’ proliferation, migration, and cell cycle progression. As a consequence, CSE could induce HPASMCs’ increased proliferation and migration, and cell cycle transition, which were suppressed by MBD2 interference. Furthermore, RNA-seq, ChIP-qPCR, and MassARRAY were conducted to find out the downstream mechanisms of MBD2 for CS-induced pulmonary vascular remodeling. Subsequently, RNA-seq revealed MBD2 might affect the transcription of BMP2 gene, which furtherly altered the expression of BMP2 protein. ChIP-qPCR demonstrated MBD2 could bind BMP2’s promotor. MassARRAY indicated that MBD2 itself could not directly affect DNA methylation. In sum, our results indicate that increased MBD2 expression promotes CS-induced pulmonary vascular remodeling. The fundamental mechanisms may be that MBD2 can bind BMP2’s promoter and downregulate its expression. Thus, MBD2 may promote the occurrence of the CS-induced PH. Frontiers Media S.A. 2022-06-16 /pmc/articles/PMC9243313/ /pubmed/35785161 http://dx.doi.org/10.3389/fonc.2022.879793 Text en Copyright © 2022 Wu, Huang, Li, Gu, Zhan, Wang, Chen, Zeng, Lv, Zhao, Xia and Xie https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Wu, Jixing Huang, Qian Li, Qinghai Gu, Yiya Zhan, Yuan Wang, Ting Chen, Jinkun Zeng, Zhilin Lv, Yongman Zhao, Jianping Xia, Jie Xie, Jungang Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension |
title | Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension |
title_full | Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension |
title_fullStr | Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension |
title_full_unstemmed | Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension |
title_short | Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension |
title_sort | increased methyl-cpg-binding domain protein 2 promotes cigarette smoke-induced pulmonary hypertension |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243313/ https://www.ncbi.nlm.nih.gov/pubmed/35785161 http://dx.doi.org/10.3389/fonc.2022.879793 |
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