دورية أكاديمية
أعرض في EDS

Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation.

التفاصيل البيبلوغرافية
العنوان: Decreased AGO2 and DCR1 in PBMCs from War Veterans with PTSD leads to diminished miRNA resulting in elevated inflammation.
المؤلفون: Bam M; Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA., Yang X; Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.; William Jennings Bryan Dorn VA Medical Center, Columbia, SC, USA., Zumbrun EE; Division of Virology, USAMRIID, Fort Detrick, MD, USA., Ginsberg JP; William Jennings Bryan Dorn VA Medical Center, Columbia, SC, USA., Leyden Q; William Jennings Bryan Dorn VA Medical Center, Columbia, SC, USA., Zhang J; Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC, USA., Nagarkatti PS; Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA., Nagarkatti M; Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
المصدر: Translational psychiatry [Transl Psychiatry] 2017 Aug 29; Vol. 7 (8), pp. e1222. Date of Electronic Publication: 2017 Aug 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: United States NLM ID: 101562664 Publication Model: Electronic Cited Medium: Internet ISSN: 2158-3188 (Electronic) Linking ISSN: 21583188 NLM ISO Abbreviation: Transl Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Original Publication: New York, NY : Nature Pub. Group
مواضيع طبية MeSH: Argonaute Proteins/*metabolism , Inflammation/*metabolism , Leukocytes, Mononuclear/*metabolism , MicroRNAs/*metabolism , Receptors, Tumor Necrosis Factor, Member 10c/*metabolism , Stress Disorders, Post-Traumatic/*metabolism, Afghan Campaign 2001- ; Down-Regulation ; GPI-Linked Proteins/metabolism ; Gulf War ; Humans ; Inflammation/complications ; Iraq War, 2003-2011 ; STAT3 Transcription Factor/metabolism ; Stress Disorders, Post-Traumatic/complications ; Veterans
مستخلص: Chronic inflammation is a characteristic of post-traumatic stress disorder (PTSD). The initiation of inflammation and molecules involved are not yet clearly understood. Here, we provide compelling evidence that the inflammation seen in PTSD may result from the dysregulated miRNA processing pathway. Using microarray analysis with a discovery group of peripheral blood mononuclear cell (PBMC) samples from War Veterans with PTSD, we found 183 significantly downregulated miRNAs, several of which target numerous genes categorized to be pro-inflammatory in nature. This observation was further confirmed in a replicate group by including more samples. Furthermore, employing RNA-sequencing, quantitative real time PCR (qRT-PCR) and in vitro experiments, we found that Argonaute 2 (AGO2) and Dicer1 (DCR1) were downregulated in PTSD and provided convincing evidence that their downregulation affects mature miRNA generation. In addition, we noted that STAT3 transcript was reduced in PTSD and this was possibly responsible for reduced AGO2 and DCR1, which in turn affected miRNA synthesis. Furthermore, we observed that activation of CD4+ T cells or monocytes led to reduced mature miRNA availability. Finally, the inflammation seen in PTSD was associated with downregulated miRNA profile. Altogether, the current study demonstrates that the chronic inflammation seen in PTSD may be a result of dysregulated miRNA biogenesis pathway due to diminished expression of the key molecules like AGO2, DCR1 and STAT3.
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معلومات مُعتمدة: R01 AI129788 United States AI NIAID NIH HHS; R01 MH094755 United States MH NIMH NIH HHS; R01 ES019313 United States ES NIEHS NIH HHS; P20 GM103641 United States GM NIGMS NIH HHS; P01 AT003961 United States AT NCCIH NIH HHS; R01 AT006888 United States AT NCCIH NIH HHS
المشرفين على المادة: 0 (AGO2 protein, human)
0 (Argonaute Proteins)
0 (GPI-Linked Proteins)
0 (MicroRNAs)
0 (Receptors, Tumor Necrosis Factor, Member 10c)
0 (STAT3 Transcription Factor)
0 (STAT3 protein, human)
0 (TNFRSF10C protein, human)
تواريخ الأحداث: Date Created: 20170830 Date Completed: 20180508 Latest Revision: 20200306
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC5611749
DOI: 10.1038/tp.2017.185
PMID: 28850112
قاعدة البيانات: MEDLINE
الوصف
تدمد:2158-3188
DOI:10.1038/tp.2017.185