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Interaction of Biochemical Processes between Chronic Obstructive Pulmonary Disease (COPD), Pulmonary Arterial Hypertension (PAH), and Coronavirus Disease 2019 (COVID-19)

Zhe Tian
Zhe Tian
 and 
Lilan Cen
Lilan Cen
   | Jun 14, 2023
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Article Category: ORIGINAL PAPER
Published Online: Jun 14, 2023
Page range: 143 - 154
Received: Jan 17, 2023
Accepted: Feb 27, 2023
DOI: https://doi.org/10.33073/pjm-2023-015
Keywords
© 2023 Zhe Tian et al., published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Fig. 1.

The mind map of the research process (https://smart.servier.com, https://www.freeimages.com).
The mind map of the research process (https://smart.servier.com, https://www.freeimages.com).

Fig. 2.

The Veen diagram of data in different data sets.
The Veen diagram of data in different data sets.

Fig. 3.

A – Bar graph of GO analysis of co-DEGs of COVID-19, COPD, PAH. BP, CC, MF-related GO terms ranked by p-values. B – Bar graph showing pathway enrichment analysis for COVID-19, COPD, and PAH. Identifying of the examination of pathways in KEGG/Reactome/Wikipathways/BioCarta database by p-value ranking.
A – Bar graph of GO analysis of co-DEGs of COVID-19, COPD, PAH. BP, CC, MF-related GO terms ranked by p-values. B – Bar graph showing pathway enrichment analysis for COVID-19, COPD, and PAH. Identifying of the examination of pathways in KEGG/Reactome/Wikipathways/BioCarta database by p-value ranking.

Fig. 4.

PPI network of COVID-19, COPD and PAH in DEGs. The network contains 59 nodes and 555 edges.
PPI network of COVID-19, COPD and PAH in DEGs. The network contains 59 nodes and 555 edges.

Fig. 5.

The network of co-DEG and TF gene interactions. Yellow nodes stand in for TF genes, while red nodes represent co-DEGs.
The network of co-DEG and TF gene interactions. Yellow nodes stand in for TF genes, while red nodes represent co-DEGs.

Fig. 6.

Cooperative TF-miRNA-DEGs network. Yellow nodes stand in for TF genes, blue nodes for miRNAs, and red nodes for co-DEGs.
Cooperative TF-miRNA-DEGs network. Yellow nodes stand in for TF genes, blue nodes for miRNAs, and red nodes for co-DEGs.

Pathway enrichment analysis of co-DEGs of COVID-19, COPD and PA.

Database type Pathways p-values Genes
KEGG Focal adhesion 5.21E-03 TNXB/PGF
Ras signaling pathway 6.88E-03 RALBP1/PGF
PI3K-Akt signaling pathway 1.55E-02 TNXB/PGF
Pathways in cancer 3.30E-02 RALBP1/PGF
Pancreatic cancer 4.10E-02 RALBP1
ECM-receptor interaction 4.74E-02 TNXB
NOD-like receptor signaling pathway 9.52E-02 GBP3
Axon guidance 9.57E-02 ABLIM3
Rap1 signaling pathway 1.10E-01 PGF
MAPK signaling pathway 1.50E-01 PGF
WikiPathways Focal Adhesion WP306 5.06E-03 TNXB/PGF
RalA downstream regulated genes WP2290 6.58E-03 RALBP1
Estrogen metabolism WP697 9.86E-03 ARSE
Focal Adhesion-PI3K-Akt-mTOR-signaling pathway WP3932 1.15E-02 TNXB/PGF
miRNA targets in ECM and membrane receptors WP2911 1.20E-02 TNXB
PI3K-Akt signaling pathway WP4172 1.43E-02 TNXB/PGF
VEGFA-VEGFR2 Signaling Pathway WP3888 2.25E-02 TNXB/PGF
Hematopoietic Stem Cell Differentiation WP2849 2.98E-02 TNXB
Pancreatic adenocarcinoma pathway WP4263 4.79E-02 RALBP1
Integrin-mediated Cell Adhesion WP185 5.42E-02 TNS1
BioCarta Ras Signaling Pathway Homo sapiens h rasPathway 1.09E-03 RALBP1
ADP-Ribosylation Factor Homo sapiens h arapPathway 1.58E-03 RALBP1
Erk and PI-3 Kinase Are Necessary for Collagen Binding in Corneal Epithelia Homo sapiens h ecmPathway 1.69E-02 TNS1
Rho cell motility signaling pathway Homo sapiens h rhoPathway 1.75E-02 RALBP1
Integrin Signaling Pathway Homo sapiens h integrinPathway 1.80E-02 TNS1
Rac 1 cell motility signaling pathway Homo sapiens h rac1Pathway 1.96E-02 RALBP1
T Cell Receptor Signaling Pathway Homo sapiens h TCR pathway 2.98E-02 RALBP1
Reactome VEGF ligand-receptor interactions Homo sapiens R-HSA-194313VEGF binds to VEGFR leading to receptor dimerization 4.39E-03 PGF
Homo sapiens R-HSA-195399 4.39E-03 PGF
The activation of arylsulfatases Homo sapiens R-HSA-1663150 7.13E-03 ARSE
DCC mediated attractive signaling Homo sapiens R-HSA-418885 7.67E-03 ABLIM3
Gamma carboxylation, hypusine formation and arylsulfatase activation Homo sapiens R-HSA-163841 2.12E-02 ARSE
Glycosphingolipid metabolism Homo sapiens R-HSA-1660662 2.23E-02 ARSE
Netrin-1 signaling Homo sapiens R-HSA-373752 2.29E-02 ABLIM3
ECM proteoglycans Homo sapiens R-HSA-3000178 2.98E-02 TNXB
Sphingolipid metabolism Homo sapiens R-HSA-428157 4.00E-02 ARSE
Interferon gamma signaling Homo sapiens R-HSA-877300 5.00E-02 GBP3

GO study of COVID-19, COPD, and PAH co-DEGs.

Category GO ID Term p-values Genes
GO-BP GO: 0060754 positive regulation of mast cell chemotaxis 2.75E-03 PGF
GO: 0060753 regulation of mast cell chemotaxis 3.30E-03 PGF
GO: 0032489 regulation of Cdc42 protein signal transduction 4.39E-03 RALBP1
GO: 0048251 elastic fiber assembly 4.39E-03 TNXB
GO: 0031401 positive regulation of protein modification process 5.88E-03 RALBP1/PGF
GO: 0030042 actin filament depolymerization 6.03E-03 MICAL3
GO: 0050930 induction of positive chemotaxis 6.03E-03 PGF
GO: 0038084 vascular endothelial growth factor signaling pathway 7.67E-03 PGF
GO: 0042327 positive regulation of phosphorylation 8.13E-03 RALBP1/PGF
GO: 0001932 regulation of protein phosphorylation 8.95E-03 RALBP1/PGF
GO-CC GO: 0015629 actin cytoskeleton 1.61E-01 ABLIM3
GO: 0062023 collagen-containing extracellular matrix 1.90E-01 TNXB
GO: 0005925 focal adhesion 1.93E-01 TNS1
GO: 0030055 cell-substrate junction 1.97E-01 TNS1
GO: 0005856 cytoskeleton 2.85E-01 ABLIM3
GO:0005634 nucleus 7.44E-01 SP140/MICAL3
GO:0043231 intracellular membrane-bounded organelle 8.22E-01 SP140/MICAL3
GO-MF GO: 0005172 vascular endothelial growth factor receptor binding 6.58E-03 PGF
GO: 0071949 FAD binding 1.37E-02 MICAL3
GO: 0042056 chemoattractant activity 1.75E-02 PGF
GO: 0016709 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen 1.95E-02 MICAL3
  GO: 0050660 flavin adenine dinucleotide binding 2.98E-02 MICAL3
GO: 0004867 serine-type endopeptidase inhibitor activity 3.25E-02 TFPI2
GO: 0008083 growth factor activity 4.68E-02 PGF
GO: 0070851 growth factor receptor binding 5.63E-02 PGF
GO: 0005126 cytokine receptor binding 5.63E-02 PGF
GO: 0004866 endopeptidase inhibitor activity 6.15E-02 TFPI2

Recommended drugs for COVID-19, COPD, PAH.

Name p-value Chemical formula Structure
Acetaminophen CTD 00005295 2.40E-03 C8H9NO2
dmnq CTD 00002569 3.21E-03 C12H10O4
2,2’,4,4’,5,5’-hexachlorobiphenyl CTD 00000731 5.57E-03 C12H4Cl6
Hexylene glycol TTD 00008431 6.58E-03 C6H14O2
Tetradioxin CTD 00006848 8.61E-03 C12H4Cl4O2
Bisindolylmaleimide IV CTD 00003116 9.31E-03 C20H13N3O2
Leukotriene C4 CTD 00007223 9.31E-03 C30H47N3O9S
Azacyclonol HL60 UP 9.55E-03 C18H21NO
Corbadrine PC3 UP 1.26E-02 C9H13NO3
Mecamylamine CTD 00006250 1.48E-02 C11H21N
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