MicroRNA-21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cells
Introduction Bronchial epithelial cell damage is an important determinant of the severity of chronic obstructive pulmonary (COPD). However, the exact molecular mechanisms underlying this cell death in COPD development are not well understood. This study investigates the involvement of microRNA-21 (m...
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| Format: | Article |
| Language: | English |
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European Publishing
2025-03-01
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| Series: | Tobacco Induced Diseases |
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| Online Access: | https://www.tobaccoinduceddiseases.org/MicroRNA-21-plays-a-role-in-exacerbating-chronic-obstructive-pulmonary-disease-by,202182,0,2.html |
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| _version_ | 1850173993897689088 |
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| author | Zhengpeng Zeng Xuelian Liu Fei Xiang Xue He Jiahui Li Hanying Liu Lihua Xie |
| author_facet | Zhengpeng Zeng Xuelian Liu Fei Xiang Xue He Jiahui Li Hanying Liu Lihua Xie |
| author_sort | Zhengpeng Zeng |
| collection | DOAJ |
| description | Introduction
Bronchial epithelial cell damage is an important determinant of the
severity of chronic obstructive pulmonary (COPD). However, the exact molecular
mechanisms underlying this cell death in COPD development are not well
understood. This study investigates the involvement of microRNA-21 (miR-21/
miRNA-21) in COPD and its underlying molecular mechanism.
Methods
A mouse model of COPD was created by exposing the mice to cigarette
smoke (CS) and injecting them with cigarette smoke extract (CSE). Both wildtype
mice and miR-21 knockout (miR-21-/-) mice were used to investigate
the role of microRNA-21 (miR-21) in exacerbating COPD. Various assays and
analyses were performed, including HE staining, tunel staining, enzyme-linked
immunosorbent assay (ELISA), flow cytometry, quantitative real-time polymerase
chain reaction (RT-qPCR), and western blotting (WB) to measure outcomes such
as the pathological morphological changes, necroptosis, apoptosis, and levels of
inflammatory factors.
Results
Our results revealed an upregulation of miR-21 in the lung tissue of
COPD model mice. Additionally, knockout of miR-21 resulted in decreased
levels of bronchial epithelial cell necroptosis and apoptosis, as evidenced by the
downregulation of tumor necrosis factor receptor 1 (TNFR1), phosphoryl-mixed
lineage kinase domain-like protein (p-MLKL) and caspase-3. This downregulation
of necroptosis and apoptosis ultimately led to a reduction of inflammatory factors
and damage-associated molecular patterns (DAMPs), such as tumor necrosis
factor-α (TNF-α), interleukin-1β (IL- 1β), and interleukin-6 (IL-6) and high
mobility group protein B1(HMGB1) in the lungs, thereby ameliorating COPD.
Conclusions
Our findings suggest that miR-21 contributes to the worsening of
chronic obstructive pulmonary disease by modulating necroptosis and apoptosis
in bronchial epithelial cells, providing a new theoretical basis for the pathogenesis
of chronic obstructive pulmonary disease. |
| format | Article |
| id | doaj-art-1bfb078db83a4ff5ad19036e06964b6a |
| institution | OA Journals |
| issn | 1617-9625 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | European Publishing |
| record_format | Article |
| series | Tobacco Induced Diseases |
| spelling | doaj-art-1bfb078db83a4ff5ad19036e06964b6a2025-08-20T02:19:44ZengEuropean PublishingTobacco Induced Diseases1617-96252025-03-0123March1910.18332/tid/202182202182MicroRNA-21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cellsZhengpeng Zeng0https://orcid.org/0009-0002-5172-2508Xuelian Liu1Fei Xiang2Xue He3Jiahui Li4Hanying Liu5Lihua Xie6Health Management Medicine Center, The Third Xiangya Hospital, Central South University, Changsha, ChinaHealth Management Medicine Center, The Third Xiangya Hospital, Central South University, Changsha, ChinaRespiratory and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, ChinaHealth Management Medicine Center, The Third Xiangya Hospital, Central South University, Changsha, ChinaChangsha Kexin Cancer Hospital, Changsha, ChinaHealth Management Medicine Center, The Third Xiangya Hospital, Central South University, Changsha, ChinaRespiratory and Critical Care Medicine, The Third Xiangya Hospital, Central South University, Changsha, ChinaIntroduction Bronchial epithelial cell damage is an important determinant of the severity of chronic obstructive pulmonary (COPD). However, the exact molecular mechanisms underlying this cell death in COPD development are not well understood. This study investigates the involvement of microRNA-21 (miR-21/ miRNA-21) in COPD and its underlying molecular mechanism. Methods A mouse model of COPD was created by exposing the mice to cigarette smoke (CS) and injecting them with cigarette smoke extract (CSE). Both wildtype mice and miR-21 knockout (miR-21-/-) mice were used to investigate the role of microRNA-21 (miR-21) in exacerbating COPD. Various assays and analyses were performed, including HE staining, tunel staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, quantitative real-time polymerase chain reaction (RT-qPCR), and western blotting (WB) to measure outcomes such as the pathological morphological changes, necroptosis, apoptosis, and levels of inflammatory factors. Results Our results revealed an upregulation of miR-21 in the lung tissue of COPD model mice. Additionally, knockout of miR-21 resulted in decreased levels of bronchial epithelial cell necroptosis and apoptosis, as evidenced by the downregulation of tumor necrosis factor receptor 1 (TNFR1), phosphoryl-mixed lineage kinase domain-like protein (p-MLKL) and caspase-3. This downregulation of necroptosis and apoptosis ultimately led to a reduction of inflammatory factors and damage-associated molecular patterns (DAMPs), such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL- 1β), and interleukin-6 (IL-6) and high mobility group protein B1(HMGB1) in the lungs, thereby ameliorating COPD. Conclusions Our findings suggest that miR-21 contributes to the worsening of chronic obstructive pulmonary disease by modulating necroptosis and apoptosis in bronchial epithelial cells, providing a new theoretical basis for the pathogenesis of chronic obstructive pulmonary disease.https://www.tobaccoinduceddiseases.org/MicroRNA-21-plays-a-role-in-exacerbating-chronic-obstructive-pulmonary-disease-by,202182,0,2.htmlcigarette smokenecroptosisapoptosismicrorna-21chronic obstructive pulmonary |
| spellingShingle | Zhengpeng Zeng Xuelian Liu Fei Xiang Xue He Jiahui Li Hanying Liu Lihua Xie MicroRNA-21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cells Tobacco Induced Diseases cigarette smoke necroptosis apoptosis microrna-21 chronic obstructive pulmonary |
| title | MicroRNA-21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cells |
| title_full | MicroRNA-21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cells |
| title_fullStr | MicroRNA-21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cells |
| title_full_unstemmed | MicroRNA-21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cells |
| title_short | MicroRNA-21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cells |
| title_sort | microrna 21 plays a role in exacerbating chronic obstructive pulmonary disease by regulating necroptosis and apoptosis in bronchial epithelial cells |
| topic | cigarette smoke necroptosis apoptosis microrna-21 chronic obstructive pulmonary |
| url | https://www.tobaccoinduceddiseases.org/MicroRNA-21-plays-a-role-in-exacerbating-chronic-obstructive-pulmonary-disease-by,202182,0,2.html |
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