ArticleMedical science monitor : international medical journal of experimental and clinical research2019
Tumor Necrosis Factor-alpha (TNF-α) Enhances miR-155-Mediated Endothelial Senescence by Targeting Sirtuin1 (SIRT1).
Article in Medical science monitor : international medical journal of experimental and clinical research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- The REDD1-NF-κB-miRNAs-eNOS/SIRT1 axis mediates obesity-induced endothelial cell senescence and hypertension.Nature communications · 2026Article
- Interpretation of the molecular mechanism and therapeutic potential of microRNA‑155 in cardiovascular and cerebrovascular diseases (Review).International journal of molecular medicine · 2026Review
- Increased Preeclampsia Risk in GDM Pregnancies: The Role of SIRT1 rs12778366 Polymorphism and Telomere Length.International journal of molecular sciences · 2025Article
- α-Bisabolol alleviates doxorubicin-induced cognitive dysfunction in rats via enhancing the hippocampal BDNF/TrKB signaling and inhibiting neuroinflammation.Frontiers in pharmacology · 2025Article
- Immune and Metabolic Mechanisms of Endothelial Dysfunction.International journal of molecular sciences · 2024Review
- Insights into Reproductive Immunology and Placental Pathology.International journal of molecular sciences · 2024Article
- Integrated bioinformatics and validation reveal PTGS2 and its related molecules to alleviate TNF-α-induced endothelial senescence.In vitro cellular & developmental biology. Animal · 2024Article
- The ability of microRNAs to regulate the immune response in ischemia/reperfusion inflammatory pathways.Genes and immunity · 2024Review
- Cellular Senescence and Extracellular Vesicles in the Pathogenesis and Treatment of Obesity-A Narrative Review.International journal of molecular sciences · 2024Review
- Article
- The Role of Sirtuin-1 (SIRT1) in the Physiology and Pathophysiology of the Human Placenta.International journal of molecular sciences · 2023Review
- Protein-Bound Uremic Toxins in Senescence and Kidney Fibrosis.Biomedicines · 2023Review
- The Uremic Toxin Indoxyl Sulfate Accelerates Senescence in Kidney Proximal Tubule Cells.Toxins · 2023Article
- MicroRNAs: a crossroad that connects obesity to immunity and aging.Immunity & ageing : I & A · 2022Review
- Inflammatory Modulation of miR-155 Inhibits Doxorubicin-Induced Testicular Dysfunction via SIRT1/FOXO1 Pathway: Insight into the Role of Acacetin and Bacillus cereus Protease.Applied biochemistry and biotechnology · 2022Article
- Delayed regression of laser-induced choroidal neovascularization in TNFα-null mice.Journal of cellular and molecular medicine · 2022Article
- Activation of SIRT-1 Pathway by Nanoceria Sheds Light on Its Ameliorative Effect on Doxorubicin-Induced Cognitive Impairment (Chemobrain): Restraining Its Neuroinflammation, Synaptic Dysplasticity and Apoptosis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- PD-L1/miR-155 Interplay in Pediatric High-Grade Glioma.Brain sciences · 2022Article
- Endothelial Cell-Derived Extracellular Vesicles Target TLR4 via miRNA-326-3p to Regulate Skin Fibroblasts Senescence.Journal of immunology research · 2022Article
- Emerging Role of Non-Coding RNAs in Senescence.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND Sirtuin1 (SIRT1) participates in a wide variety of cellular processes, but the molecular mechanism remains largely unknown. miR-155 is an element of the inflammatory signaling pathway in atherosclerosis. Therefore, we tested the hypothesis that TNF-alpha stimulates miR-155 to target SIRT1 and thereby regulates endothelial senescence, and we also explored the function of miR-155 as a regulator of cardiovascular diseases. MATERIAL AND METHODS TNF-alpha was used to stimulate human umbilical vein endothelial cells (HUVECs), after which protein and gene expression were assessed via Western blotting and RT-qPCR. miR-155 targeting of SIRT1 was confirmed via luciferase reporter assays, while MTT and senescence-associated ß-galactosidase (SA-ß-gal) assays were used for quantifying cellular proliferation and senescence. RESULTS We found that miR-155 was upregulated in response to TNF-alpha treatment, in addition to inducing marked changes in SIRT1/FoxO-1/p21 pathway protein level. When we overexpressed miR-155 mimics, SIRT1 was markedly reduced, whereas miR-155 inhibition had the opposite effect in TNF-alpha-treated cells. We additionally confirmed that miR-155 was able to directly bind to SIRT1 3'-UTR, and that inhibition of miR-155 reduced the ability of TNF-alpha to induce senescence in HUVECs, thereby leading to their enhanced proliferation. Simvastatin was associated with suppression of miR-155 expression in HUVECs following TNF-alpha treatment, and with a corresponding reduction in TNF-alpha-induced senescence, whereas miR-155 overexpression had the opposite effect. CONCLUSIONS Our findings suggest that TNF-alpha upregulates miR-155, which then targets SIRT1, suppressing its expression and driving HUVEC apoptosis. Simvastatin disrupted this senescence mechanism via the miR-155/SIRT1/FoxO-1/p21 pathway signaling. Hence, miR-155 is a possible therapeutic approach to endothelial senescence in the development of cardiovascular diseases.
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Registered trials
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.