Potential biomarkers and therapeutic targets of idiopathic pulmonary arterial hypertension
© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Physiological reports - 10(2022), 1 vom: 04. Jan., Seite e15101 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
He, Wenjun [VerfasserIn] |
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| Links: |
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| Themen: |
Biomarker |
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| Anmerkungen: |
Date Completed 04.04.2022 Date Revised 05.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.14814/phy2.15101 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a GEO | |
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| 700 | 1 | |a Chen, Lingdan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Chunli |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Wenju |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jian |e verfasserin |4 aut | |
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