Analysis of the polarization states of the alveolar macrophages in chronic obstructive pulmonary disease samples based on miRNA-mRNA network signatures

Shen, Wen; Wang, Shukun; Wang, Ruili; Zhang, Yang; Tian, Hong; Yang, Xiaolei; Wei, Wei

doi:10.21037/atm-21-3815

Cited by 10 publications

(7 citation statements)

References 64 publications

(55 reference statements)

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“… 52 Besides, there was also a great difference in the composition of macrophages between COPD patients, smokers, and non-smokers; the proportion of M1 macrophages in smokers and COPD patients was lower than that of M0 and M2 macrophages. 53 The findings above further illustrated the importance of M0 macrophages to COPD. It should be noted that the differences in polarized macrophages between COPD patients and healthy controls were not statistically significant in this work.…”

Section: Discussionmentioning

confidence: 66%

A Macrophage-Related Gene Signature for Identifying COPD Based on Bioinformatics and ex vivo Experiments

Zhang,

Yu,

Wang

et al. 2023

JIR

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Background This study aims to investigate the association between immune cells and the development of COPD, while providing a new method for the diagnosis of COPD according to the changes in immune microenvironment. Methods In this study, the “CIBERSORT” algorithm was used to estimate the tissue infiltration of 22 types of immune cells in GSE20257 and GSE10006. The “limma” package was used for differentially expressed analysis. The key modules associated with vital immune cells were identified using WGCNA. GO and KEGG enrichment analysis revealed the biological functions of the candidate genes. Ultimately, a novel diagnostic prediction model was constructed via machine learning methods and multivariate logistic regression analysis based on GSE20257. Furthermore, we examined the stability of the model on one internal test set (GSE10006), three external test sets (GSE8545, GSE57148 and GSE76925), one single-cell transcriptome dataset (GSE167295), macrophages (THP-M cells) and lung tissue from COPD patients. Results M0 macrophages (AUC > 0.7 in GSE20257 and GSE10006) were considered as the most important immune cells through exploring the immune microenvironment landscapes in COPD patients and healthy controls. The differentially expressed genes from GSE20257 and GSE10006 were divided into six and five modules via WGCNA, respectively. The green module in GSE20257 (cor = 0.41, P < 0.001) and the brown module in GSE10006 (cor = 0.67, P < 0.001) were highly correlated with M0 macrophages and were selected as key modules. Forty-one intersected genes obtained from two modules were primarily involved in regulation of cytokine production, regulation of innate immune response, specific granule, phagosome, lysosome, ferroptosis, and other biological processes. On the basis of the candidate genetic markers further characterized via the “Boruta” and “LASSO” algorithm for COPD, a diagnostic model comprising CLEC5A, FTL and SLC2A3 was constructed, which could accurately distinguish COPD patients from healthy controls in multiple datasets. GSE20257 as the training set has an AUC of 0.916. The AUCs of the internal test set and three external test sets were 0.873, 0.932, 0.675 and 0.688, respectively. Single-cell sequencing analysis suggested that CLEC5A, FTL and SLC2A3 were expressed in macrophages from COPD patients. The expressions of CLEC5A, FTL and SLC2A3 were up-regulated in THP-M cells and lung tissue from COPD patients. Conclusion According to the variations of immune microenvironment in COPD patients, we constructed and validated a novel macrophage M0-associated diagnostic model with satisfactory predictive value. CLEC5A, FTL and SLC2A3 are expected to be promising targets of immunotherapy in COPD.

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Section: Discussionmentioning

confidence: 66%

A Macrophage-Related Gene Signature for Identifying COPD Based on Bioinformatics and ex vivo Experiments

Zhang,

Yu,

Wang

et al. 2023

JIR

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“…Moreover, overexpression of circRNA_SLC8A1 inhibited the apoptosis, decreased Cleaved-caspase-3 protein expression in Mtb-infected macrophages, and promoted the survival of Mtb in macrophages, whereas overexpression of miR-20b-5p significantly reversed the effects of circRNA_SLC8A1 overexpression on Mtb-infected macrophages. Shen et al 31 reported that miR-20b-5p was higher expression in M2 macrophages, compared with M1 macrophages. Overexpressing miR-20b-5p suppressed the progression of chronic obstructive pulmonary disease by inhibiting macrophages to M1 phenotype by suppressing inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-κB pathway

Li,

Gao,

Zhang

et al. 2024

Sci Rep

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Macrophages act as the first immune defense line of the host against Mycobacterium tuberculosis (Mtb). A previous study showed that circRNA_SLC8A1 was significantly upregulated in Mtb-infected macrophages, but its regulatory mechanism in anti-tuberculosis infection is unclear. Therefore, this study aimed to investigate the role of circRNA_SLC8A1 in the anti-tuberculosis activity of macrophages. We showed that circRNA_SLC8A1 was upregulated in tuberculosis patients. Moreover, the binding sites of miR-20b-5p on circRNA_SLC8A1 and Sequestosome 1 (SQSTM1/p62) mRNA were predicted by StarBase and verified by the double luciferase reporter gene assay. Next, we found that miR-20b-5p expression was decreased, while SQSTM1 protein expression was increased in a time- and dose-dependent manner in the human macrophage U937 in response to Mtb infection. Furthermore, circRNA_SLC8A1 overexpression vector (circRNA_SLC8A1) or shRNA (sh-circRNA_SLC8A1) and/or miR-20b-5p mimic or inhibitor and/or SQSTM1 overexpression vector (SQSTM1) or small interfering RNA (si-SQSTM1) or its corresponding control were transfected into Mtb-infected macrophages. Results showed that overexpression of circRNA_SLC8A1 or miR-20b-5p inhibitor promoted the secretion of pro-inflammatory factors IL-1β, IL-6, and TNF-α, increased Nitric Oxide (NO) content and inducible nitric oxide synthase (iNOS) expression, inhibited Reactive oxygen species (ROS) production. Cleaved-caspase-3 protein expression, and cell apoptosis, and promoted Mtb survival. Silencing SQSTM1 inhibited secretion of pro-inflammatory factors and activation of the NF-κB pathway. Overexpression of miR‐20b‐5p blocked the promoting of circ‐SLC8A1 on SQSTM1 protein expression. In summary, circRNA_SLC8A1 sponged miR‐20b‐5p to upregulate SQSTM1/p62 expression and promoted Mtb survival in macrophages through the NF-κB signaling pathway.

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“…For COVID-19-associated genes, we referred the PubChem ( https://pubchem.ncbi.nlm.nih.gov/#query=covid-19 ), CTD ( http://ctdbase.org/ ), DisGeNET ( https://www.disgenet.org/covid/diseases/summary/ ), baillielab net ( https://baillielab.net/maic/covid19 ) and KEGG DISEASE ( https://www.genome.jp/kegg/disease/ ) databases and data sets of ( Grant et al, 2021 ; Blanco-Melo et al, 2020 ; Mahmud et al, 2021 ; Singh et al, 2021 ; Overmyer et al, 2021 ; Mo et al, 2021 ). Regarding COPD-related genes, we considered DisGeNET ( https://www.disgenet.org/ ), CTD ( http://ctdbase.org/ ) and GeneCards ( https://www.genecards.org/ ) databases and data sets of ( O'Beirne et al, 2020 ; Han et al, 2021 ; Morrow et al, 2017 ; Hu et al, 2018 ; Raman et al, 2009 ; Huang et al, 2019 ; Morrow et al, 2019 ; Shen et al, 2021 ). These selected data sets above represent different clinical samples of COVID-19/COPD, specifically including alveolar lavage fluid, lung tissue, airway and peripheral blood.…”

Section: Methodsmentioning

confidence: 99%

Host Factor Interaction Networks Identified by Integrative Bioinformatics Analysis Reveals Therapeutic Implications in COPD Patients With COVID-19

Zheng

Wang

et al. 2021

Front. Pharmacol.

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Background: The COVID-19 pandemic poses an imminent threat to humanity, especially for those who have comorbidities. Evidence of COVID-19 and COPD comorbidities is accumulating. However, data revealing the molecular mechanism of COVID-19 and COPD comorbid diseases is limited.Methods: We got COVID-19/COPD -related genes from different databases by restricted screening conditions (top500), respectively, and then supplemented with COVID-19/COPD-associated genes (FDR<0.05, |LogFC|≥1) from clinical sample data sets. By taking the intersection, 42 co-morbid host factors for COVID-19 and COPD were finally obtained. On the basis of shared host factors, we conducted a series of bioinformatics analysis, including protein-protein interaction analysis, gene ontology and pathway enrichment analysis, transcription factor-gene interaction network analysis, gene-microRNA co-regulatory network analysis, tissue-specific enrichment analysis and candidate drug prediction.Results: We revealed the comorbidity mechanism of COVID-19 and COPD from the perspective of host factor interaction, obtained the top ten gene and 3 modules with different biological functions. Furthermore, we have obtained the signaling pathways and concluded that dexamethasone, estradiol, progesterone, and nitric oxide shows effective interventions.Conclusion: This study revealed host factor interaction networks for COVID-19 and COPD, which could confirm the potential drugs for treating the comorbidity, ultimately, enhancing the management of the respiratory disease.

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Analysis of the polarization states of the alveolar macrophages in chronic obstructive pulmonary disease samples based on miRNA-mRNA network signatures

Cited by 10 publications

References 64 publications

A Macrophage-Related Gene Signature for Identifying COPD Based on Bioinformatics and ex vivo Experiments

A Macrophage-Related Gene Signature for Identifying COPD Based on Bioinformatics and ex vivo Experiments

circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-κB pathway

Host Factor Interaction Networks Identified by Integrative Bioinformatics Analysis Reveals Therapeutic Implications in COPD Patients With COVID-19

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