ArticleJournal of neuroinflammation2021
Tonicity-responsive enhancer-binding protein promotes diabetic neuroinflammation and cognitive impairment via upregulation of lipocalin-2.
Article in Journal of neuroinflammation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- Astrocytic LCN2 mediates pathological crosstalk with neurons to promote neuronal loss in sepsis-associated encephalopathy.Cell death and differentiation · 2026Article
- Icariin Alleviates Diabetes-Associated Cognitive Dysfunction Through Modulation of LCN2-MEK/ERK Signaling-Associated Neuroinflammation.CNS neuroscience & therapeutics · 2026Article
- The NFAT5-AR Axis Is Associated with Hyperosmolarity, Renal Dysfunction, and Neutrophil-Related Inflammatory Markers in Diabetic Retinopathy.International journal of molecular sciences · 2026Article
- 17β-Trenbolone Increases the Release of Lipocalin 2 via the Brain-Liver Axis and Causes Alzheimer's Disease-Like Symptoms in CSDS-Induced Mice.Molecular neurobiology · 2025Article
- Article
- Microglial galectin-3 increases with aging in the mouse hippocampus.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Mechanisms of time-restricted feeding-induced neuroprotection and neuronal plasticity in ischemic stroke as a function of circadian rhythm.Experimental neurology · 2025Review
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Inhibition of ANGPTL8 protects against diabetes-associated cognitive dysfunction by reducing synaptic loss via the PirB signaling pathway.Journal of neuroinflammation · 2024Article
- Binding of RAGE and RIPK1 induces cognitive deficits in chronic hyperglycemia-derived neuroinflammation.CNS neuroscience & therapeutics · 2024Article
- Intermittent Fasting Reduces Neuroinflammation and Cognitive Impairment in High-Fat Diet-Fed Mice by Downregulating Lipocalin-2 and Galectin-3.Nutrients · 2024Article
- Gandouling Regulates Ferroptosis and Improves Neuroinflammation in Wilson's Disease Through the LCN2/NLRP3 Signaling Pathway.Journal of inflammation research · 2024Article
- TMT-Based Proteomics Analysis Revealed the Protein Changes in Perirenal Fat from Obese Rabbits.International journal of molecular sciences · 2023Article
- Article
- TonEBP expression is essential in the IL-1β-induced migration and invasion of human A549 lung cancer cells.Oncology research · 2023Article
- Oxidative stress: The nexus of obesity and cognitive dysfunction in diabetes.Frontiers in endocrinology · 2023Review
- The Role of Iron Overload in Diabetic Cognitive Impairment: A Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Review
- Article
- Lipocalin-2 Deficiency Reduces Hepatic and Hippocampal Triggering Receptor Expressed on Myeloid Cells-2 Expressions in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.Brain sciences · 2022Article
- Zi Shen Wan Fang Attenuates Neuroinflammation and Cognitive FunctionFrontiers in pharmacology · 2022Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDiabetic individuals have increased circulating inflammatory mediators which are implicated as underlying causes of neuroinflammation and memory deficits. Tonicity-responsive enhancer-binding protein (TonEBP) promotes diabetic neuroinflammation. However, the precise role of TonEBP in the diabetic brain is not fully understood.
methodsWe employed a high-fat diet (HFD)-only fed mice or HFD/streptozotocin (STZ)-treated mice in our diabetic mouse models. Circulating TonEBP and lipocalin-2 (LCN2) levels were measured in type 2 diabetic subjects. TonEBP haploinsufficient mice were used to investigate the role of TonEBP in HFD/STZ-induced diabetic mice. In addition, RAW 264.7 macrophages were given a lipopolysaccharide (LPS)/high glucose (HG) treatment. Using a siRNA, we examined the effects of TonEBP knockdown on RAW264 cell' medium/HG-treated mouse hippocampal HT22 cells.
resultsCirculating TonEBP and LCN2 levels were higher in experimental diabetic mice or type 2 diabetic patients with cognitive impairment. TonEBP haploinsufficiency ameliorated the diabetic phenotypes including adipose tissue macrophage infiltrations, neuroinflammation, blood-brain barrier leakage, and memory deficits. Systemic and hippocampal LCN2 proteins were reduced in diabetic mice by TonEBP haploinsufficiency. TonEBP (+ / -) mice had a reduction of hippocampal heme oxygenase-1 (HO-1) expression compared to diabetic wild-type mice. In particular, we found that TonEBP bound to the LCN2 promoter in the diabetic hippocampus, and this binding was abolished by TonEBP haploinsufficiency. Furthermore, TonEBP knockdown attenuated LCN2 expression in lipopolysaccharide/high glucose-treated mouse hippocampal HT22 cells.
conclusionsThese findings indicate that TonEBP may promote neuroinflammation and cognitive impairment via upregulation of LCN2 in diabetic mice.
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