ArticleClinical and translational medicine2021
Cyclosporine modulates neutrophil functions via the SIRT6-HIF-1α-glycolysis axis to alleviate severe ulcerative colitis.
Article in Clinical and translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.
- Neutrophil extracellular traps as a potential therapeutic target in inflammatory bowel disease: a systematic review and meta-analysis.Frontiers in immunology · 2026Pooled it
- Effects of cuproptosis and its application in inflammatory bowel disease (Review).International journal of molecular medicine · 2026Review
- A Review on the Molecular Dynamics of EnterotypeInternational journal of molecular sciences · 2026Review
- Exploring the Treatment of Cinnamomum Cassia Leaf Extract in Ulcerative Colitis: Network Pharmacology and In Vitro Investigations.Plants (Basel, Switzerland) · 2026Article
- NEAT1 modulates neutrophil functions via glycolysis to restrain mucosal inflammation in ulcerative colitis.Frontiers in immunology · 2026Article
- Neutrophil extracellular traps in gout: from immune defense to pathological dynamic equilibrium.Frontiers in immunology · 2026Review
- Glucolipid metabolic dysfunction in ankylosing spondylitis: inflammatory mechanisms, immune-metabolic crosstalk and therapeutic implications of natural products and traditional Chinese medicine.Frontiers in immunology · 2026Review
- HIF-1α at the intersection of hypoxia, ferroptosis-associated stress, and cell death crosstalk in osteomyelitis.Frontiers in cell and developmental biology · 2026Review
- A preclinical investigation into the potential associations of geraniin with ulcerative colitis alleviation through integrated multi-omics andFrontiers in medicine · 2026Article
- The central regulator HIF-1α in digestive system pathologies: inflammation and cancer.Frontiers in immunology · 2026Review
- Transcriptomic exploration of key genes related to mitochondria and ferroptosis in inflammatory bowel disease and experimental validation.Scientific reports · 2025Article
- A "Mesoporous Oxygen Chamber" Scaffold with Antibacterial and Early Immunomodulatory Effect for Promoting Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RVG engineered extracellular vesicles-transmitted miR-137 improves autism by modulating glucose metabolism and neuroinflammation.Molecular psychiatry · 2025Article
- Quercetin alleviates acute pancreatitis by modulating glycolysis and mitochondrial function via PFKFB3 inhibition.Cellular and molecular life sciences : CMLS · 2025Article
- Neutrophils and NETs in Pathophysiology and Treatment of Inflammatory Bowel Disease.International journal of molecular sciences · 2025Review
- Targeting PFKFB3 to restore glucose metabolism in acute pancreatitis via nanovesicle delivery.Molecular medicine (Cambridge, Mass.) · 2025Article
- The multifaceted role of sirtuins in inflammatory bowel diseases.American journal of physiology. Gastrointestinal and liver physiology · 2025Review
- KunMingShanHaiTang formula reprograms macrophage metabolism and promotes M2 polarization via the HIF-1α pathway to alleviate ulcerative colitis symptoms in a rat model.Journal of bioenergetics and biomembranes · 2025Article
- Asparagine transporter supports macrophage inflammation via histone phosphorylation.Science advances · 2025Article
- Mesenchymal stem cell-derived extracellular vesicles alleviate autism by regulating microglial glucose metabolism reprogramming and neuroinflammation through PD-1/PD-L1 interaction.Journal of nanobiotechnology · 2025Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCyclosporine A (CsA) is routinely used to treat patients with steroid-refractory acute severe ulcerative colitis (ASUC). Here, we studied the underlying mechanisms of CsA-mediated alleviation in ASUC patients.
methodsNeutrophil functions including expression of cytokines, apoptosis, and migration were measured by qRT-PCR, flow cytometry, and Transwell assay. Dynamic changes of glycolysis and tricarboxylic acid (TCA) cycle were measured by a Seahorse extracellular flux analyzer. Gene differences were determined and verified by RNA sequencing, qRT-PCR, and Western blotting. Small interfering RNA and inhibitors were used to knock down Sirtuin 6 (SIRT6) in HL-60 cells and block expression of SIRT6, hypoxia-inducible factor-1α (HIF-1α), and pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4) in neutrophils.
resultsWe found that HIF-1α expression and glycolysis significantly increased, while the release of IL-8, myeloperoxidase (MPO) and reactive oxygen species (ROS), the apoptosis, and ability of migration markedly decreased in neutrophils of ASUC patients who responded to CsA (Response group) compared with those who did not respond to CsA (Nonresponse group). We also observed that CsA-induced functional alternation of neutrophils was initiated through suppressing SIRT6 expression, which is responsible for expression of the downstream signaling molecules (e.g., HIF-1α, PFKFB3) and PDK4 ubiquitination, leading to fueling neutrophil glycolysis and TCA cycle. Furthermore, blockage of SIRT6 signaling demonstrated to be the same functional changes as CsA to decrease the migration of neutrophils.
conclusionsThe data reveal a novel mechanism of CsA in alleviating ASUC by promoting neutrophil HIF-1α expression and restricting excessive neutrophil activation in a SIRT6-HIF-1α-glycolysis axis, suggesting SIRT6 as a candidate target for maintaining mucosal homeostasis and treating intestinal inflammation.
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