Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease

Abstract Background Chronic obstructive pulmonary disease (COPD) has impacted approximately 390 million people worldwide and the morbidity is increasing every year. However, due to the poor treatment efficacy of COPD, exploring novel treatment has become the hotpot of study on COPD. Endothelial prog...

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Main Authors: Wenhua Wang, Huaihuai Peng, Menghao Zeng, Jie Liu, Guibin Liang, Zhihui He
Format: Article
Language:English
Published: BMC 2023-12-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-023-04735-x
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author Wenhua Wang
Huaihuai Peng
Menghao Zeng
Jie Liu
Guibin Liang
Zhihui He
author_facet Wenhua Wang
Huaihuai Peng
Menghao Zeng
Jie Liu
Guibin Liang
Zhihui He
author_sort Wenhua Wang
collection DOAJ
description Abstract Background Chronic obstructive pulmonary disease (COPD) has impacted approximately 390 million people worldwide and the morbidity is increasing every year. However, due to the poor treatment efficacy of COPD, exploring novel treatment has become the hotpot of study on COPD. Endothelial progenitor cells (EPCs) aging is a possible molecular way for COPD development. We aimed to explore the effector whether intravenous administration of EPCs has therapeutic effects in COPD mice. Methods COPD mice model was induced by cigarette smoke exposure and EPCs were injected intravenously to investigate their effects on COPD mice. At day 127, heart, liver, spleen, lung and kidney tissues of mice were harvested. The histological effects of EPCs intervention on multiple organs of COPD mice were detected by morphology assay. Quantitative real-time PCR and Western blotting were used to detect the effect of EPCs intervention on the expression of multi-organ senescence-related indicators. And we explored the effect of EPCs systematically intervening on senescence-related USP7/p300 pathway. Results Compared with COPD group, senescence-associated β-galactosidase activity was decreased, protein and mRNA expression of p16 was down-regulated, while protein and mRNA expression of cyclin D1 and TERT were up-regulated of multiple organs, including lung, heart, liver, spleen and kidney in COPD mice after EPCs system intervention. But the morphological alterations of the tissues described above in COPD mice failed to be reversed. Mechanistically, EPCs systemic administration inhibited the expression of mRNA and protein of USP7 and p300 in multiple organs of COPD mice, exerting therapeutic effects. Conclusions EPCs administration significantly inhibited the senescence of multiple organs in COPD mice via down-regulating USP7/p300 pathway, which presents a possibility of EPCs therapy for COPD.
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spelling doaj.art-7c7b3626db7e4d4e9fbb4e41dc7b2a9a2023-12-10T12:29:41ZengBMCJournal of Translational Medicine1479-58762023-12-0121111910.1186/s12967-023-04735-xEndothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary diseaseWenhua Wang0Huaihuai Peng1Menghao Zeng2Jie Liu3Guibin Liang4Zhihui He5Department of Intensive Care Unit, The Third Xiangya Hospital, Central South UniversityDepartment of Intensive Care Unit, Hunan Province Directly Affiliated Traditional Chinese Medicine HospitalDepartment of Intensive Care Unit, The Third Xiangya Hospital, Central South UniversityDepartment of Intensive Care Unit, The Third Xiangya Hospital, Central South UniversityDepartment of Intensive Care Unit, The Third Xiangya Hospital, Central South UniversityDepartment of Intensive Care Unit, The Third Xiangya Hospital, Central South UniversityAbstract Background Chronic obstructive pulmonary disease (COPD) has impacted approximately 390 million people worldwide and the morbidity is increasing every year. However, due to the poor treatment efficacy of COPD, exploring novel treatment has become the hotpot of study on COPD. Endothelial progenitor cells (EPCs) aging is a possible molecular way for COPD development. We aimed to explore the effector whether intravenous administration of EPCs has therapeutic effects in COPD mice. Methods COPD mice model was induced by cigarette smoke exposure and EPCs were injected intravenously to investigate their effects on COPD mice. At day 127, heart, liver, spleen, lung and kidney tissues of mice were harvested. The histological effects of EPCs intervention on multiple organs of COPD mice were detected by morphology assay. Quantitative real-time PCR and Western blotting were used to detect the effect of EPCs intervention on the expression of multi-organ senescence-related indicators. And we explored the effect of EPCs systematically intervening on senescence-related USP7/p300 pathway. Results Compared with COPD group, senescence-associated β-galactosidase activity was decreased, protein and mRNA expression of p16 was down-regulated, while protein and mRNA expression of cyclin D1 and TERT were up-regulated of multiple organs, including lung, heart, liver, spleen and kidney in COPD mice after EPCs system intervention. But the morphological alterations of the tissues described above in COPD mice failed to be reversed. Mechanistically, EPCs systemic administration inhibited the expression of mRNA and protein of USP7 and p300 in multiple organs of COPD mice, exerting therapeutic effects. Conclusions EPCs administration significantly inhibited the senescence of multiple organs in COPD mice via down-regulating USP7/p300 pathway, which presents a possibility of EPCs therapy for COPD.https://doi.org/10.1186/s12967-023-04735-xCOPDSenescenceEPCsSystemic administrationUSP7p300
spellingShingle Wenhua Wang
Huaihuai Peng
Menghao Zeng
Jie Liu
Guibin Liang
Zhihui He
Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease
Journal of Translational Medicine
COPD
Senescence
EPCs
Systemic administration
USP7
p300
title Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease
title_full Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease
title_fullStr Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease
title_full_unstemmed Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease
title_short Endothelial progenitor cells systemic administration alleviates multi-organ senescence by down-regulating USP7/p300 pathway in chronic obstructive pulmonary disease
title_sort endothelial progenitor cells systemic administration alleviates multi organ senescence by down regulating usp7 p300 pathway in chronic obstructive pulmonary disease
topic COPD
Senescence
EPCs
Systemic administration
USP7
p300
url https://doi.org/10.1186/s12967-023-04735-x
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