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...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-06-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.879793/full |
| _version_ | 1811243454019141632 |
|---|---|
| author | Jixing Wu Qian Huang Qinghai Li Yiya Gu Yuan Zhan Ting Wang Jinkun Chen Zhilin Zeng Yongman Lv Jianping Zhao Jie Xia Jungang Xie |
| author_facet | Jixing Wu Qian Huang Qinghai Li Yiya Gu Yuan Zhan Ting Wang Jinkun Chen Zhilin Zeng Yongman Lv Jianping Zhao Jie Xia Jungang Xie |
| author_sort | Jixing Wu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T14:08:42Z |
| format | Article |
| id | doaj.art-6c18ea30cf7847b1b41cc719d7f7b932 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T14:08:42Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-6c18ea30cf7847b1b41cc719d7f7b9322022-12-22T03:30:00ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-06-011210.3389/fonc.2022.879793879793Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary HypertensionJixing Wu0Qian Huang1Qinghai Li2Yiya Gu3Yuan Zhan4Ting Wang5Jinkun Chen6Zhilin Zeng7Yongman Lv8Jianping Zhao9Jie Xia10Jungang Xie11Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, ChinaDepartment of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory Disease, Thoracic Disease Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Science, Western University, London, ON, CanadaDepartment and Institute of Infectious Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHealth Management Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaPulmonary 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.https://www.frontiersin.org/articles/10.3389/fonc.2022.879793/fullpulmonary hypertensionMBD2cigarette smokepulmonary artery smooth muscle cellsBMP2pulmonary vascular remodeling |
| spellingShingle | Jixing Wu Qian Huang Qinghai Li Yiya Gu Yuan Zhan Ting Wang Jinkun Chen Zhilin Zeng Yongman Lv Jianping Zhao Jie Xia Jungang Xie Increased Methyl-CpG-Binding Domain Protein 2 Promotes Cigarette Smoke-Induced Pulmonary Hypertension Frontiers in Oncology pulmonary hypertension MBD2 cigarette smoke pulmonary artery smooth muscle cells BMP2 pulmonary vascular remodeling |
| 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 | pulmonary hypertension MBD2 cigarette smoke pulmonary artery smooth muscle cells BMP2 pulmonary vascular remodeling |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.879793/full |
| work_keys_str_mv | AT jixingwu increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT qianhuang increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT qinghaili increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT yiyagu increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT yuanzhan increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT tingwang increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT jinkunchen increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT zhilinzeng increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT yongmanlv increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT jianpingzhao increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT jiexia increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension AT jungangxie increasedmethylcpgbindingdomainprotein2promotescigarettesmokeinducedpulmonaryhypertension |