Trial reportEMBO molecular medicine2015
Modulation of TNF-α mRNA stability by human antigen R and miR181s in sepsis-induced immunoparalysis.
Trial report in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- The involvement of regulatory non-coding RNAs in sepsis: a systematic review.Critical care (London, England) · 2016Pooled it
- The LINC00920/miR-6834-3p/CPN1 Axis Modulates Immune Dysregulation in Sepsis-Associated Acute Kidney Injury and Serves as a Diagnostic Biomarker.Biochemical genetics · 2026Article
- Steroid hormone ouabain cooperates with NaActa pharmaceutica Sinica. B · 2026Article
- Article
- Mechanisms mediating effects of cardiotonic steroids in mammalian blood cells.Frontiers in pharmacology · 2025Review
- Predicting microRNAs and their Target Genes Involved in Sepsis Pathogenesis by using Bioinformatics Methods.Current pharmaceutical design · 2025Article
- The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways.Genes and immunity · 2024Review
- Human Antigen R, a Myofibroblast-Specific Target in Treating Cardiac Fibrosis.JACC. Basic to translational science · 2024Article
- Inflammation as a driver of hematological malignancies.Frontiers in oncology · 2024Review
- Salivary miRNA Profiles in COVID-19 Patients with Different Disease Severities.International journal of molecular sciences · 2023Article
- Na, K-ATPase α1 cooperates with its endogenous ligand to reprogram immune microenvironment of lung carcinoma and promotes immune escape.Science advances · 2023Article
- NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Transcriptomic clustering of critically ill COVID-19 patients.The European respiratory journal · 2023Article
- Modes of action and diagnostic value of miRNAs in sepsis.Frontiers in immunology · 2022Review
- Small RNA Expression Profiling Reveals hsa-miR-181d-5p Downregulation Associated With TNF-α Overexpression in Sjögren's Syndrome Patients.Frontiers in immunology · 2022Article
- MicroRNA as an Early Biomarker of Neonatal Sepsis.Frontiers in pediatrics · 2022Review
- Post-transcriptional control of T-cell cytokine production: Implications for cancer therapy.Immunology · 2021Review
- Columbianadin Dampens In Vitro Inflammatory Actions and Inhibits Liver Injury via Inhibition of NF-κB/MAPKs: Impacts onAntioxidants (Basel, Switzerland) · 2021Article
- Poly(ADP-ribosyl)ation enhances HuR oligomerization and contributes to pro-inflammatory gene mRNA stabilization.Cellular and molecular life sciences : CMLS · 2021Article
- MicroRNA-199-3p up-regulation enhances chondrocyte proliferation and inhibits apoptosis in knee osteoarthritis via DNMT3A repression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunoparalysis is an important pathological mechanism in sepsis. However, an effective small molecule therapy is lacking. Here, we show that ouabain, a Na(+),K(+)-ATPase ligand, can reverse immunoparalysis in vitro, in vivo, and in clinical samples. Notably, the effect of ouabain was critically dependent on TNF-α expression. However, ouabain had opposing effects on the stability of TNF-α mRNA: Ouabain triggered miR-181 transcription, which promoted TNF-α mRNA degradation and induced immunoparalysis, and ouabain triggered the nuclear export of human antigen R (HuR), which stabilized TNF-α mRNA and suppressed immuno-paralysis. Interestingly, because the miR-181 binding site is located within the HuR binding site in the 3'-untranslated region of TNF-α, in ouabain-treated cells, HuR competed with miR-181 for binding to TNF-α mRNA and recruited TNF-α mRNA to stress granules, thereby stabilizing TNF-α mRNA and reversing immunoparalysis. Ouabain also induced GM-CSF and interferon-γ expression in a HuR-dependent manner. Hence, the fine-tuning of TNF-α mRNA stability by HuR and miR181 plays a crucial role in immunoparalysis, and Na(+),K(+)-ATPase ligands are promising agents for immunoparalysis therapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.