TY - JOUR
T1 - A Potent Histone Deacetylase Inhibitor MPT0E028 Mitigates Emphysema Severity via Components of the Hippo Signaling Pathway in an Emphysematous Mouse Model
AU - Yeh, Lu-Yang
AU - Fang, Yu-Ting
AU - Lee, Hong-Sheng
AU - Liu, Chia-Hao
AU - Chen, You-Yin
AU - Lo, Yu-Chun
AU - Laiman, Vincent
AU - Liou, Jing-Ping
AU - Chung, Kian Fan
AU - Chuang, Hsiao-Chi
AU - Lin, Chien-Huang
PY - 2022/5
Y1 - 2022/5
N2 - BackgroundChronic 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 MethodsA 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.Results50 mg/kg BW of the MPT0E028 significantly decreased the tidal volume in emphysematous mice (p < 0.05). Emphysema severity was significantly reduced from 26.65% (PPE only) to 13.83% (50 mg/kg BW of the MPT0E028). Total cell counts, neutrophils, lymphocytes, and eosinophils significantly decreased with both 25 and 50 mg/kg BW of the MPT0E028 (p < 0.05). Also, 50 mg/kg BW of the MPT0E028 significantly decreased the levels of KC, TNF-α, and IL-6 in lung tissues and serum (p < 0.05). Expressions of p-TAZ/TAZ in lung tissues significantly decreased with 50 mg/kg BW of the MPT0E028 (p < 0.05). Expressions of p53 significantly decreased in alveolar regions with 50 mg/kg BW of the MPT0E028 (p < 0.05), and the expression of SPC increased in alveolar regions with 50 mg/kg BW of the MPT0E028 (p < 0.05).ConclusionsOur 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.
AB - BackgroundChronic 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 MethodsA 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.Results50 mg/kg BW of the MPT0E028 significantly decreased the tidal volume in emphysematous mice (p < 0.05). Emphysema severity was significantly reduced from 26.65% (PPE only) to 13.83% (50 mg/kg BW of the MPT0E028). Total cell counts, neutrophils, lymphocytes, and eosinophils significantly decreased with both 25 and 50 mg/kg BW of the MPT0E028 (p < 0.05). Also, 50 mg/kg BW of the MPT0E028 significantly decreased the levels of KC, TNF-α, and IL-6 in lung tissues and serum (p < 0.05). Expressions of p-TAZ/TAZ in lung tissues significantly decreased with 50 mg/kg BW of the MPT0E028 (p < 0.05). Expressions of p53 significantly decreased in alveolar regions with 50 mg/kg BW of the MPT0E028 (p < 0.05), and the expression of SPC increased in alveolar regions with 50 mg/kg BW of the MPT0E028 (p < 0.05).ConclusionsOur 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.
U2 - 10.3389/fmed.2022.794025
DO - 10.3389/fmed.2022.794025
M3 - Article
VL - 9
JO - Frontiers in Medicine
JF - Frontiers in Medicine
SN - 2296-858X
ER -