Verification of the role of spiperone in the treatment of COPD through bioinformatics analysis

Zhu, Donglan; Chen, Lin; Huang, Jinfu; Zhong, Xiaoning

doi:10.1016/j.intimp.2021.108308

Cited by 2 publications

(2 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zhu et al have confirmed the role of spiperone in COPD through bioinformatics analysis. 15 It has been widely used to find hub genes to explore the potential mechanism of COPD progression. 16 Five ferroptosis-related hub genes are found to affect COPD by regulating ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

Cai,

Chen,

Zhu

et al. 2023

COPD

View full text Add to dashboard Cite

Background: Chronic obstructive pulmonary disease (COPD) is a persistent chronic bronchitis disease, and its potential biomarkers have not been fully expounded. This study aims to explore the role of Guanine nucleotide binding protein like-3-like (GNL3L) in COPD induced by cigarette smoking (CS) in vivo. Methods: Two microarray datasets of COPD were selected to screen differentially expressed genes (DEGs). A protein-protein interaction network was constructed to find hub genes. The COPD model was conducted using CS/LPS-induced mouse and cigarette smoke extract induced human bronchial epithelial cells. The pathological changes of lung tissue in mice were observed by hematoxylin-eosin staining and mean linear intercept. Cell viability was measured by CCK8 assay. Oxidative stress-related indicators, inflammatory factors, and ATM/p53 related-proteins were assessed using ELISA and Western blot. Results: In this study, there were 110 common DEGs identified from the two datasets (GSE5058 and GSE38974). The key gene GNL3L was the optimal indicator to distinguish between samples with COPD and healthy controls. Through the in vivo and in vitro experiments, GNL3L knockdown significantly improved the pathological features of CS/LPS-induced COPD mice, promoted cell viability, inhibited inflammation (IL-1β, IL-8, and TNF-α), oxidative stress (MDA, SOD, and CAT), and ATM/p53 related-proteins (ATM, p53, and p21). Conclusion: GNL3L is a novel biomarker of COPD, and knockdown of GNL3L participates in the progression of COPD by inhibiting ATM/p53 pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

Cai,

Chen,

Zhu

et al. 2023

COPD

View full text Add to dashboard Cite

show abstract

“…Previously, it was shown that spiperone can reverse key changes in gene expression associated with regulation of hydrolase activity pathway in epithelial cells and monocytes subjected to cigarette smoke stimulation. 73 Therefore, further studies are required to understand the mechanisms underlying the action of spiperone in pulmonary injury repair and pathogenesis of COPD.…”

Section: Discussionmentioning

confidence: 99%

Spiperone Stimulates Regeneration in Pulmonary Endothelium Damaged by Cigarette Smoke and Lipopolysaccharide

Скурихин¹,

Першина²,

Zhukova³

et al. 2021

COPD

View full text Add to dashboard Cite

Background Endothelial dysfunction and destruction of the pulmonary microcirculation are important pathogenic factors in chronic obstructive pulmonary disease (COPD). In COPD, bronchial obstruction is associated with endothelial dysfunction. Thus, new pharmacological treatment options aimed at restoring the pulmonary endothelium represent a clinical need in COPD therapy. Notch1 has been shown to protect cells against apoptosis, inflammation, and oxidative stress caused by cigarette smoke extract (CSE). Therefore, drug which effect on Notch1 may be a potential therapeutic target for COPD in the future. Methods In this study, we assessed the potential of spiperone to mediate regeneration of pulmonary endothelium in model of pulmonary emphysema induced by a CSE and lipopolysaccharide (LPS) in female C57BL/6 mice. Results Spiperone increased the number of capillaries as well as the expression of the CD31 in the alveolar tissue compared to the controls. Moreover, application of spiperone prevented alveolar wall destruction (DI), and reduced the area of emphysema. Lastly, we demonstrated that spiperone positively influenced mobilization and migration of endothelial progenitor cells (EPC, CD45 − CD34 + CD31 + ), CD309 + -endothelial cells, and angiogenesis precursors (CD45 − CD117 + CD309 + ) into the lung. Spiperone administration significantly reduced the number Notch1 positive CD309 + -endothelial cells and Notch1+ EPCs. Conclusion Overall, our results suggest that spiperone mediates endothelial regeneration in an animal model of COPD. Thus, it could represent a novel therapeutic approach for treatment of emphysema associated with COPD.

show abstract

Verification of the role of spiperone in the treatment of COPD through bioinformatics analysis

Cited by 2 publications

References 26 publications

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

Knockdown of GNL3L Alleviates the Progression of COPD Through Inhibiting the ATM/p53 Pathway

Spiperone Stimulates Regeneration in Pulmonary Endothelium Damaged by Cigarette Smoke and Lipopolysaccharide

Contact Info

Product

Resources

About