A Potent Histone Deacetylase Inhibitor MPT0E028 Mitigates Emphysema Severity via Components of the Hippo Signaling Pathway in an Emphysematous Mouse Model.
COPD
HDAC
TAZ
alveolar
apoptosis
inflammation
Journal
Frontiers in medicine
ISSN: 2296-858X
Titre abrégé: Front Med (Lausanne)
Pays: Switzerland
ID NLM: 101648047
Informations de publication
Date de publication:
2022
2022
Historique:
received:
13
10
2021
accepted:
21
04
2022
entrez:
6
6
2022
pubmed:
7
6
2022
medline:
7
6
2022
Statut:
epublish
Résumé
Chronic obstructive pulmonary disease (COPD) is a major cause of chronic mortality. The objective of this study was to investigate the therapeutic potential of a novel potent histone deacetylase (HDAC) inhibitor MPT0E028 on emphysema. A mouse model of porcine pancreatic elastase (PPE)-induced emphysema was orally administered 0, 25, or 50 mg/kg body weight (BW) of the MPT0E028 five times/week for 3 weeks. Pulmonary function, mean linear intercept (MLI), chest CT, inflammation, yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), surfactant protein C (SPC), T1-α, p53, and sirtuin 1 (SIRT1) levels were examined. 50 mg/kg BW of the MPT0E028 significantly decreased the tidal volume in emphysematous mice ( Our study showed that the potent HDAC inhibitor MPT0E028 reduced the severity and inflammation of emphysema with improvement in lung function, which could be regulated by Hippo signaling pathway. The MPT0E028 may have therapeutic potential for emphysema.
Sections du résumé
Background
UNASSIGNED
Chronic obstructive pulmonary disease (COPD) is a major cause of chronic mortality. The objective of this study was to investigate the therapeutic potential of a novel potent histone deacetylase (HDAC) inhibitor MPT0E028 on emphysema.
Materials and Methods
UNASSIGNED
A mouse model of porcine pancreatic elastase (PPE)-induced emphysema was orally administered 0, 25, or 50 mg/kg body weight (BW) of the MPT0E028 five times/week for 3 weeks. Pulmonary function, mean linear intercept (MLI), chest CT, inflammation, yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), surfactant protein C (SPC), T1-α, p53, and sirtuin 1 (SIRT1) levels were examined.
Results
UNASSIGNED
50 mg/kg BW of the MPT0E028 significantly decreased the tidal volume in emphysematous mice (
Conclusions
UNASSIGNED
Our study showed that the potent HDAC inhibitor MPT0E028 reduced the severity and inflammation of emphysema with improvement in lung function, which could be regulated by Hippo signaling pathway. The MPT0E028 may have therapeutic potential for emphysema.
Identifiants
pubmed: 35665319
doi: 10.3389/fmed.2022.794025
pmc: PMC9157428
doi:
Types de publication
Journal Article
Langues
eng
Pagination
794025Informations de copyright
Copyright © 2022 Yeh, Fang, Lee, Liu, Chen, Lo, Laiman, Liou, Chung, Chuang and Lin.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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