PU.1 alleviates the inhibitory effects of cigarette smoke on endothelial progenitor cell function and lung-homing through Wnt/β-catenin and CXCL12/CXCR4 pathways
Introduction Endothelial progenitor cells (EPCs) dysfunction is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The transcription factor PU.1 is essential for the maintenance of stem/progenitor cell homeostasis. However, the role of PU.1 in COPD and its effects on EPC f...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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European Publishing
2024-01-01
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| Series: | Tobacco Induced Diseases |
| Subjects: | |
| Online Access: | https://www.tobaccoinduceddiseases.org/PU-1-alleviates-the-inhibitory-effects-of-cigarette-smoke-non-endothelial-progenitor,174661,0,2.html |
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| _version_ | 1832587248931962880 |
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| author | Xue He<sup>+</sup> Yanan Cui<sup>+</sup> Tiao Li Lijuan Luo Zihang Zeng Yiming Ma Yan Chen |
| author_facet | Xue He<sup>+</sup> Yanan Cui<sup>+</sup> Tiao Li Lijuan Luo Zihang Zeng Yiming Ma Yan Chen |
| author_sort | Xue He<sup>+</sup> |
| collection | DOAJ |
| description | Introduction
Endothelial progenitor cells (EPCs) dysfunction is involved in the
pathogenesis of chronic obstructive pulmonary disease (COPD). The transcription
factor PU.1 is essential for the maintenance of stem/progenitor cell homeostasis.
However, the role of PU.1 in COPD and its effects on EPC function and lunghoming,
remain unclear. This study aimed to explore the protective activity of
PU.1 and the underlying mechanisms in a cigarette smoke extract (CSE)-induced
emphysema mouse model.
Methods
C57BL/6 mice were treated with CSE to establish a murine emphysema
model and injected with overexpressed PU.1 or negative control adeno-associated
virus. Morphometry of lung slides, lung function, and apoptosis of lung tissues
were evaluated. Immunofluorescence co-localization was used to analyze EPCs
homing into the lung. Flow cytometry was performed to detect EPC count in
lung tissues and bone marrow (BM). The angiogenic ability of BM-derived EPCs
cultured in vitro was examined by tube formation assay. We determined the
expression levels of PU.1, β-catenin, C-X-C motif ligand 12 (CXCL12), C-X-C
motif receptor 4 (CXCR4), stem cell antigen-1 (Sca-1), and stemness genes.
Results
CSE exposure significantly reduced the expression of PU.1 in mouse lung
tissues, BM, and BM-derived EPCs. PU.1 overexpression attenuated CSE-induced
emphysematous changes, lung function decline, and apoptosis. In emphysematous
mice, PU.1 overexpression markedly reversed the decreased proportion of EPCs
in BM and promoted the lung-homing of EPCs. The impaired angiogenic ability
of BM-derived EPCs induced by CSE could be restored by the overexpression of
PU.1. In addition, PU.1 upregulation evidently reversed the decreased expression
of β-catenin, CXCL12, CXCR4, Scal-1, and stemness genes in mouse lung tissues,
BM, and BM-derived EPCs after CSE exposure.
Conclusions
PU.1 alleviates the inhibitory effects of CSE on EPC function and lunghoming
via activating the canonical Wnt/β-catenin pathway and CXCL12/CXCR4
axis. While further research is needed, our research may indicate a potential
therapeutic target for COPD patients. |
| format | Article |
| id | doaj-art-d1f99f8049fc4ecfad2d089d848fe0ab |
| institution | Kabale University |
| issn | 1617-9625 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | European Publishing |
| record_format | Article |
| series | Tobacco Induced Diseases |
| spelling | doaj-art-d1f99f8049fc4ecfad2d089d848fe0ab2025-01-24T15:26:49ZengEuropean PublishingTobacco Induced Diseases1617-96252024-01-0122January11310.18332/tid/174661174661PU.1 alleviates the inhibitory effects of cigarette smoke on endothelial progenitor cell function and lung-homing through Wnt/β-catenin and CXCL12/CXCR4 pathwaysXue He<sup>+</sup>0Yanan Cui<sup>+</sup>1Tiao Li2Lijuan Luo3Zihang Zeng4Yiming Ma5Yan Chen6Department of Thoracic Surgery, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, ChinaIntroduction Endothelial progenitor cells (EPCs) dysfunction is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The transcription factor PU.1 is essential for the maintenance of stem/progenitor cell homeostasis. However, the role of PU.1 in COPD and its effects on EPC function and lunghoming, remain unclear. This study aimed to explore the protective activity of PU.1 and the underlying mechanisms in a cigarette smoke extract (CSE)-induced emphysema mouse model. Methods C57BL/6 mice were treated with CSE to establish a murine emphysema model and injected with overexpressed PU.1 or negative control adeno-associated virus. Morphometry of lung slides, lung function, and apoptosis of lung tissues were evaluated. Immunofluorescence co-localization was used to analyze EPCs homing into the lung. Flow cytometry was performed to detect EPC count in lung tissues and bone marrow (BM). The angiogenic ability of BM-derived EPCs cultured in vitro was examined by tube formation assay. We determined the expression levels of PU.1, β-catenin, C-X-C motif ligand 12 (CXCL12), C-X-C motif receptor 4 (CXCR4), stem cell antigen-1 (Sca-1), and stemness genes. Results CSE exposure significantly reduced the expression of PU.1 in mouse lung tissues, BM, and BM-derived EPCs. PU.1 overexpression attenuated CSE-induced emphysematous changes, lung function decline, and apoptosis. In emphysematous mice, PU.1 overexpression markedly reversed the decreased proportion of EPCs in BM and promoted the lung-homing of EPCs. The impaired angiogenic ability of BM-derived EPCs induced by CSE could be restored by the overexpression of PU.1. In addition, PU.1 upregulation evidently reversed the decreased expression of β-catenin, CXCL12, CXCR4, Scal-1, and stemness genes in mouse lung tissues, BM, and BM-derived EPCs after CSE exposure. Conclusions PU.1 alleviates the inhibitory effects of CSE on EPC function and lunghoming via activating the canonical Wnt/β-catenin pathway and CXCL12/CXCR4 axis. While further research is needed, our research may indicate a potential therapeutic target for COPD patients.https://www.tobaccoinduceddiseases.org/PU-1-alleviates-the-inhibitory-effects-of-cigarette-smoke-non-endothelial-progenitor,174661,0,2.htmlpu.1cigarette smoke extractendothelial progenitor cellwnt/β-catenin pathwaycxcl12/cxcr4 axis |
| spellingShingle | Xue He<sup>+</sup> Yanan Cui<sup>+</sup> Tiao Li Lijuan Luo Zihang Zeng Yiming Ma Yan Chen PU.1 alleviates the inhibitory effects of cigarette smoke on endothelial progenitor cell function and lung-homing through Wnt/β-catenin and CXCL12/CXCR4 pathways Tobacco Induced Diseases pu.1 cigarette smoke extract endothelial progenitor cell wnt/β-catenin pathway cxcl12/cxcr4 axis |
| title | PU.1 alleviates the inhibitory effects of cigarette smoke
on endothelial progenitor cell function and lung-homing
through Wnt/β-catenin and CXCL12/CXCR4 pathways |
| title_full | PU.1 alleviates the inhibitory effects of cigarette smoke
on endothelial progenitor cell function and lung-homing
through Wnt/β-catenin and CXCL12/CXCR4 pathways |
| title_fullStr | PU.1 alleviates the inhibitory effects of cigarette smoke
on endothelial progenitor cell function and lung-homing
through Wnt/β-catenin and CXCL12/CXCR4 pathways |
| title_full_unstemmed | PU.1 alleviates the inhibitory effects of cigarette smoke
on endothelial progenitor cell function and lung-homing
through Wnt/β-catenin and CXCL12/CXCR4 pathways |
| title_short | PU.1 alleviates the inhibitory effects of cigarette smoke
on endothelial progenitor cell function and lung-homing
through Wnt/β-catenin and CXCL12/CXCR4 pathways |
| title_sort | pu 1 alleviates the inhibitory effects of cigarette smoke on endothelial progenitor cell function and lung homing through wnt β catenin and cxcl12 cxcr4 pathways |
| topic | pu.1 cigarette smoke extract endothelial progenitor cell wnt/β-catenin pathway cxcl12/cxcr4 axis |
| url | https://www.tobaccoinduceddiseases.org/PU-1-alleviates-the-inhibitory-effects-of-cigarette-smoke-non-endothelial-progenitor,174661,0,2.html |
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