Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease
Abstract Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease. COPD is associated with accelerated lung aging. Circadian clock is believed to play important roles in COPD. Although the circadian molecular clock regulates cellular senescence, there is no information avail...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Pulmonary Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12890-022-02237-y |
| _version_ | 1811304626482315264 |
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| author | Lingling Li Min Zhang Chunyang Zhao Yusheng Cheng Chuanmei Liu Minhua Shi |
| author_facet | Lingling Li Min Zhang Chunyang Zhao Yusheng Cheng Chuanmei Liu Minhua Shi |
| author_sort | Lingling Li |
| collection | DOAJ |
| description | Abstract Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease. COPD is associated with accelerated lung aging. Circadian clock is believed to play important roles in COPD. Although the circadian molecular clock regulates cellular senescence, there is no information available regarding the impact of COPD. The aim of this study is to investigate the role of the circadian clock protein BMAL1 and CLOCK in cellular senescence in order to understand the cellular mechanisms of accelerated aging of COPD. Bmal1 and Clock levels were assessed in the plasma samples of non-smokers, smokers, and patients with COPD. The regulation of ciracadian clock expression and cell senescence by cigarette smoke extract (CSE) was studied in vitro, and small interfering RNA (siRNA) and overexpression of Bmal1 or Clock were employed to investigate the role of circadian clock on cell senescence. Herein, patients with COPD showed lower Bmal1 and Clock expression in the plasma. Interestingly, CSE exposure contributed to the increased cell senescence, decreased Clock and Bmal1 in human bronchial epithelial cells (Beas-2B cells). We found that knockdown of Clock or Bmal1 lead to upregulation of cell senescence in Beas-2B cells, while overexpression of Clock or Bmal1 inhibited cell senescence in Beas-2B cells, which is through the MAPK pathways. Therefore, our findings indicated that Bmal1 or Clock deficiency may be a significant factor to increase cellular senescence of the lung to develop COPD. |
| first_indexed | 2024-04-13T08:10:46Z |
| format | Article |
| id | doaj.art-cc90818d3cc2437c911e0184d6ec60e3 |
| institution | Directory Open Access Journal |
| issn | 1471-2466 |
| language | English |
| last_indexed | 2024-04-13T08:10:46Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pulmonary Medicine |
| spelling | doaj.art-cc90818d3cc2437c911e0184d6ec60e32022-12-22T02:55:00ZengBMCBMC Pulmonary Medicine1471-24662022-11-0122111410.1186/s12890-022-02237-yCircadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary diseaseLingling Li0Min Zhang1Chunyang Zhao2Yusheng Cheng3Chuanmei Liu4Minhua Shi5Department of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Soochow UniversityDepartment of Emergency, Yijishan Hospital, Wannan Medical CollegeDepartment of Pulmonary and Critical Care Medicine, Yijishan Hospital, Wannan Medical CollegeDepartment of Pulmonary and Critical Care Medicine, Yijishan Hospital, Wannan Medical CollegeDepartment of Pulmonary and Critical Care Medicine, Yijishan Hospital, Wannan Medical CollegeDepartment of Pulmonary and Critical Care Medicine, The Second Affiliated Hospital of Soochow UniversityAbstract Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease. COPD is associated with accelerated lung aging. Circadian clock is believed to play important roles in COPD. Although the circadian molecular clock regulates cellular senescence, there is no information available regarding the impact of COPD. The aim of this study is to investigate the role of the circadian clock protein BMAL1 and CLOCK in cellular senescence in order to understand the cellular mechanisms of accelerated aging of COPD. Bmal1 and Clock levels were assessed in the plasma samples of non-smokers, smokers, and patients with COPD. The regulation of ciracadian clock expression and cell senescence by cigarette smoke extract (CSE) was studied in vitro, and small interfering RNA (siRNA) and overexpression of Bmal1 or Clock were employed to investigate the role of circadian clock on cell senescence. Herein, patients with COPD showed lower Bmal1 and Clock expression in the plasma. Interestingly, CSE exposure contributed to the increased cell senescence, decreased Clock and Bmal1 in human bronchial epithelial cells (Beas-2B cells). We found that knockdown of Clock or Bmal1 lead to upregulation of cell senescence in Beas-2B cells, while overexpression of Clock or Bmal1 inhibited cell senescence in Beas-2B cells, which is through the MAPK pathways. Therefore, our findings indicated that Bmal1 or Clock deficiency may be a significant factor to increase cellular senescence of the lung to develop COPD.https://doi.org/10.1186/s12890-022-02237-yCircadian clockChronic obstructive Pulmonary Disease (COPD)SmokeSenescence |
| spellingShingle | Lingling Li Min Zhang Chunyang Zhao Yusheng Cheng Chuanmei Liu Minhua Shi Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease BMC Pulmonary Medicine Circadian clock Chronic obstructive Pulmonary Disease (COPD) Smoke Senescence |
| title | Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease |
| title_full | Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease |
| title_fullStr | Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease |
| title_full_unstemmed | Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease |
| title_short | Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease |
| title_sort | circadian clock gene clock bmal1 regulates cellular senescence in chronic obstructive pulmonary disease |
| topic | Circadian clock Chronic obstructive Pulmonary Disease (COPD) Smoke Senescence |
| url | https://doi.org/10.1186/s12890-022-02237-y |
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