Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension

Abstract Background Peripheral blood mononuclear cells (PBMCs) play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). However, the specific roles of PBMCs in the development and progression of idiopathic PAH (IPAH) have not been fully understood. Methods Here, different...

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Main Authors: Wenjun He, Xi Su, Lingdan Chen, Chunli Liu, Wenju Lu, Tao Wang, Jian Wang
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Physiological Reports
Subjects:
Online Access:https://doi.org/10.14814/phy2.15101
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author Wenjun He
Xi Su
Lingdan Chen
Chunli Liu
Wenju Lu
Tao Wang
Jian Wang
author_facet Wenjun He
Xi Su
Lingdan Chen
Chunli Liu
Wenju Lu
Tao Wang
Jian Wang
author_sort Wenjun He
collection DOAJ
description Abstract Background Peripheral blood mononuclear cells (PBMCs) play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). However, the specific roles of PBMCs in the development and progression of idiopathic PAH (IPAH) have not been fully understood. Methods Here, differentially expressed genes (DEGs) of PBMCs or lung tissues between IPAH patients and healthy controls were identified via bioinformatics analysis of Gene Expression Omnibus (GEO) datasets GSE33463 and GSE48149, respectively. Subsequently, extensive target prediction and network analysis were performed to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms, and pathway enrichment for DEGs. Co‐expressed DEGs between PBMCs and lung tissues coupled with corresponding predicted miRNAs involved in PAH were also assessed. We identified 251 DEGs in PBMCs and 151 DEGs in lung tissue samples from IPAH. PDK4, RBPMS2, and PDE5A expression were altered in both PBMCs and lung tissues from IPAH patients compared to healthy control. Results CXCL8, JUN, TLR8, IL1B, and TLR7 could be implicated as the hub genes in PBMCs, whereas ENO1, STAT1, CXCL10, GPI, and IRF1 in lung tissues. Finally, co‐expressed DEGs of PDK4, RBPMS2, and PDE5A coupled with corresponding predicted miRNAs, especially miR‐103a‐3p, miR‐185‐5p, and miR‐515‐5p, are significantly associated with IPAH. Conclusion Our findings collectively suggest that the expression levels of PDK4, RBPMS2, and PDE5A in PBMCs are associated with the expression of these genes in lung tissues. Thus, these molecules may serve as potential circulating biomarkers and/or possible therapeutic targets for IPAH.
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spelling doaj.art-cd7c3289350040c49710dde5361284b02022-12-21T17:33:39ZengWileyPhysiological Reports2051-817X2022-01-01101n/an/a10.14814/phy2.15101Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertensionWenjun He0Xi Su1Lingdan Chen2Chunli Liu3Wenju Lu4Tao Wang5Jian Wang6State Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular Diseases National Clinical Research Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaState Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular Diseases National Clinical Research Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaState Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular Diseases National Clinical Research Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaState Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular Diseases National Clinical Research Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaState Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular Diseases National Clinical Research Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaState Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular Diseases National Clinical Research Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaState Key Laboratory of Respiratory Diseases Guangdong Key Laboratory of Vascular Diseases National Clinical Research Center for Respiratory Diseases Guangzhou Institute of Respiratory Health The First Affiliated Hospital of Guangzhou Medical University Guangzhou ChinaAbstract Background Peripheral blood mononuclear cells (PBMCs) play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). However, the specific roles of PBMCs in the development and progression of idiopathic PAH (IPAH) have not been fully understood. Methods Here, differentially expressed genes (DEGs) of PBMCs or lung tissues between IPAH patients and healthy controls were identified via bioinformatics analysis of Gene Expression Omnibus (GEO) datasets GSE33463 and GSE48149, respectively. Subsequently, extensive target prediction and network analysis were performed to assess protein–protein interaction (PPI) networks, Gene Ontology (GO) terms, and pathway enrichment for DEGs. Co‐expressed DEGs between PBMCs and lung tissues coupled with corresponding predicted miRNAs involved in PAH were also assessed. We identified 251 DEGs in PBMCs and 151 DEGs in lung tissue samples from IPAH. PDK4, RBPMS2, and PDE5A expression were altered in both PBMCs and lung tissues from IPAH patients compared to healthy control. Results CXCL8, JUN, TLR8, IL1B, and TLR7 could be implicated as the hub genes in PBMCs, whereas ENO1, STAT1, CXCL10, GPI, and IRF1 in lung tissues. Finally, co‐expressed DEGs of PDK4, RBPMS2, and PDE5A coupled with corresponding predicted miRNAs, especially miR‐103a‐3p, miR‐185‐5p, and miR‐515‐5p, are significantly associated with IPAH. Conclusion Our findings collectively suggest that the expression levels of PDK4, RBPMS2, and PDE5A in PBMCs are associated with the expression of these genes in lung tissues. Thus, these molecules may serve as potential circulating biomarkers and/or possible therapeutic targets for IPAH.https://doi.org/10.14814/phy2.15101biomarkergene analysisGEOIPAH
spellingShingle Wenjun He
Xi Su
Lingdan Chen
Chunli Liu
Wenju Lu
Tao Wang
Jian Wang
Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension
Physiological Reports
biomarker
gene analysis
GEO
IPAH
title Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension
title_full Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension
title_fullStr Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension
title_full_unstemmed Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension
title_short Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension
title_sort potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension
topic biomarker
gene analysis
GEO
IPAH
url https://doi.org/10.14814/phy2.15101
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