Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users
Jie Jia,1,2 Ji-Qun Yang,3 Ying-Rong Du,3 Yu Xu,2 Deshenyue Kong,1,2 Xiu-Ling Zhang,3 Jun-Hong Mao,1,2 Gui-Fang Hu,3 Kun-Hua Wang,1,2,4 Yi-Qun Kuang1,2 1NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032,...
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Dove Medical Press
2022-06-01
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author | Jia J Yang JQ Du YR Xu Y Kong D Zhang XL Mao JH Hu GF Wang KH Kuang YQ |
author_facet | Jia J Yang JQ Du YR Xu Y Kong D Zhang XL Mao JH Hu GF Wang KH Kuang YQ |
author_sort | Jia J |
collection | DOAJ |
description | Jie Jia,1,2 Ji-Qun Yang,3 Ying-Rong Du,3 Yu Xu,2 Deshenyue Kong,1,2 Xiu-Ling Zhang,3 Jun-Hong Mao,1,2 Gui-Fang Hu,3 Kun-Hua Wang,1,2,4 Yi-Qun Kuang1,2 1NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032, People’s Republic of China; 2Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 3Third People’s Hospital of Kunming City/Drug Rehabilitation Hospital of Kunming City, Kunming, 650041, People’s Republic of China; 4School of Medicine, Yunnan University, Kunming, 650500, People’s Republic of ChinaCorrespondence: Yi-Qun Kuang; Kun-Hua Wang, NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032, People’s Republic of China, Email yq610433@hotmail.com; wangkunhua1964@126.comBackground: Hypertension is a common complication in injection drug users (IDU), especially a high proportion of resistant hypertension occurs among them. However, the involving mechanisms remain largely unknown.Methods: We here investigated the key signaling moieties in resistant hypertension in drug users. Analyses were performed with high-throughput transcriptomic sequencing data of peripheral blood from individuals with drug-sensitive hypertension (Ctrl-DS), IDU with resistant hypertension (IDU-DR), and IDU with sensitive hypertension (IDU-DS).Results: We showed that 17 and 1 genes in IDU-DS, 48 and 4 genes in IDU-DR were upregulated and downregulated compared Ctrl-DS, and 2 and 4 genes were upregulated and downregulated in IDU-DR compared with IDU-DS, respectively (p ≤ 0.01 and |log2(FC)| ≥ 1). Differentially expressed genes (DEGs) between Ctrl-DS and IDU-DS were mainly involved in Gene ontology terms of immunoglobulin complex and blood microparticle. DEGs between IDU-DS and IDU-DR were mainly involved in immune system process and immunoglobulin complex. DEGs between Ctrl-DS and IDU-DR were mainly involved in immunoglobulin complex, blood microparticle and cytoplasmic vesicle lumen. We identified 2 gene clusters (brown modules, MEbrown; turquoise module, MEturquoise) correlated with IDU-DR and a gene cluster (magenta module, MEmagenta) correlated with IDU-DS by weighted gene co-expression network analysis (WGCNA). Functional analysis demonstrated that pathways of focal adhesion and focalin-1-rich granule lumen were involved in the development of IDU-DR, and the cytosolic large ribosomal subunit may relate to IDU-DR. Further, immune cell infiltration analysis demonstrated that the abundance of dendritic cells (DCs), natural Treg cells (nTreg), and exhausted T cells (Tex) in IDU-DR and IDU-DS, naïve CD8+ T cells in IDU-DS was significantly different compared with that in Ctrl-DS. The abundance of cytotoxic T cells (Tc) was significantly different between IDU-DS and IDU-DR.Conclusion: Our findings indicated a potential function of immunoregulation mechanisms for resistant hypertension.Keywords: drug use, hypertension, treatment-resistant, transcriptome, immunoregulation |
first_indexed | 2024-04-12T18:10:22Z |
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issn | 1178-7031 |
language | English |
last_indexed | 2024-04-12T18:10:22Z |
publishDate | 2022-06-01 |
publisher | Dove Medical Press |
record_format | Article |
series | Journal of Inflammation Research |
spelling | doaj.art-b9f6c91d64b84d11a0e84a6f04bde8da2022-12-22T03:21:51ZengDove Medical PressJournal of Inflammation Research1178-70312022-06-01Volume 153409342075843Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug UsersJia JYang JQDu YRXu YKong DZhang XLMao JHHu GFWang KHKuang YQJie Jia,1,2 Ji-Qun Yang,3 Ying-Rong Du,3 Yu Xu,2 Deshenyue Kong,1,2 Xiu-Ling Zhang,3 Jun-Hong Mao,1,2 Gui-Fang Hu,3 Kun-Hua Wang,1,2,4 Yi-Qun Kuang1,2 1NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032, People’s Republic of China; 2Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 3Third People’s Hospital of Kunming City/Drug Rehabilitation Hospital of Kunming City, Kunming, 650041, People’s Republic of China; 4School of Medicine, Yunnan University, Kunming, 650500, People’s Republic of ChinaCorrespondence: Yi-Qun Kuang; Kun-Hua Wang, NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, 650032, People’s Republic of China, Email yq610433@hotmail.com; wangkunhua1964@126.comBackground: Hypertension is a common complication in injection drug users (IDU), especially a high proportion of resistant hypertension occurs among them. However, the involving mechanisms remain largely unknown.Methods: We here investigated the key signaling moieties in resistant hypertension in drug users. Analyses were performed with high-throughput transcriptomic sequencing data of peripheral blood from individuals with drug-sensitive hypertension (Ctrl-DS), IDU with resistant hypertension (IDU-DR), and IDU with sensitive hypertension (IDU-DS).Results: We showed that 17 and 1 genes in IDU-DS, 48 and 4 genes in IDU-DR were upregulated and downregulated compared Ctrl-DS, and 2 and 4 genes were upregulated and downregulated in IDU-DR compared with IDU-DS, respectively (p ≤ 0.01 and |log2(FC)| ≥ 1). Differentially expressed genes (DEGs) between Ctrl-DS and IDU-DS were mainly involved in Gene ontology terms of immunoglobulin complex and blood microparticle. DEGs between IDU-DS and IDU-DR were mainly involved in immune system process and immunoglobulin complex. DEGs between Ctrl-DS and IDU-DR were mainly involved in immunoglobulin complex, blood microparticle and cytoplasmic vesicle lumen. We identified 2 gene clusters (brown modules, MEbrown; turquoise module, MEturquoise) correlated with IDU-DR and a gene cluster (magenta module, MEmagenta) correlated with IDU-DS by weighted gene co-expression network analysis (WGCNA). Functional analysis demonstrated that pathways of focal adhesion and focalin-1-rich granule lumen were involved in the development of IDU-DR, and the cytosolic large ribosomal subunit may relate to IDU-DR. Further, immune cell infiltration analysis demonstrated that the abundance of dendritic cells (DCs), natural Treg cells (nTreg), and exhausted T cells (Tex) in IDU-DR and IDU-DS, naïve CD8+ T cells in IDU-DS was significantly different compared with that in Ctrl-DS. The abundance of cytotoxic T cells (Tc) was significantly different between IDU-DS and IDU-DR.Conclusion: Our findings indicated a potential function of immunoregulation mechanisms for resistant hypertension.Keywords: drug use, hypertension, treatment-resistant, transcriptome, immunoregulationhttps://www.dovepress.com/transcriptomic-profiling-reveals-underlying-immunoregulation-mechanism-peer-reviewed-fulltext-article-JIRdrug usehypertensiontreatment-resistanttranscriptomeimmunoregulation |
spellingShingle | Jia J Yang JQ Du YR Xu Y Kong D Zhang XL Mao JH Hu GF Wang KH Kuang YQ Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users Journal of Inflammation Research drug use hypertension treatment-resistant transcriptome immunoregulation |
title | Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users |
title_full | Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users |
title_fullStr | Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users |
title_full_unstemmed | Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users |
title_short | Transcriptomic Profiling Reveals Underlying Immunoregulation Mechanisms of Resistant Hypertension in Injection Drug Users |
title_sort | transcriptomic profiling reveals underlying immunoregulation mechanisms of resistant hypertension in injection drug users |
topic | drug use hypertension treatment-resistant transcriptome immunoregulation |
url | https://www.dovepress.com/transcriptomic-profiling-reveals-underlying-immunoregulation-mechanism-peer-reviewed-fulltext-article-JIR |
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