ArticleNature communications2020
MD2 activation by direct AGE interaction drives inflammatory diabetic cardiomyopathy.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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Who cites it
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 135 citations in OpenAlex.
- Investigating the biomarkers of diabetic-cardiomyopathy with the high mobility group box-1 as a potential anti-inflammatory therapeutic target: Systematic Review and meta-analysis.Frontiers in endocrinology · 2025Pooled it
- What is the impact of ferroptosis on diabetic cardiomyopathy: a systematic review.Heart failure reviews · 2024Pooled it
- Inflammatory signalling in diabetic cardiomyopathy: molecular mechanisms and potential therapeutic strategies.Nature reviews. Cardiology · 2026Review
- N-Terminal Basic Helix and S120 Phosphorylation Cooperatively Regulate Nuclear Localization of UBE2A/B in Mechanotransduction.Biology · 2026Article
- When sugar takes your breath away: how diabetes accelerates COPD progression.EMBO molecular medicine · 2026Article
- Blocking AGEs reduces airway epithelial viral susceptibility in diabetes-exacerbated COPD.EMBO molecular medicine · 2026Article
- Hepatocyte BDNF Acts as a Novel Immune Checkpoint to Restrain TLR4-Mediated Acute Hepatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- OTUD6A in Airway Epithelial Cells Exacerbates Allergic Asthma by Promoting Airway Inflammation and Airway Remodeling Through Deubiquitination of hResistin/mRELMα.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Brain-derived neurotrophic factor and the derived dodecapeptide function as Toll-like receptor 4 antagonists in acute lung injury.Nature communications · 2026Article
- Advanced Glycation End-Products Contribute to Delayed Diabetic Corneal Epithelial Wound Healing via the TLR4 Signaling.Investigative ophthalmology & visual science · 2026Article
- The pivotal role of immunometabolism in diabetic neuropathy and its potential therapeutic strategies.Frontiers in endocrinology · 2026Review
- Advanced glycation end products and RAGE signaling in diabetic cardiomyopathy: distinct mechanisms, human evidence, and translational barriers.Frontiers in cardiovascular medicine · 2026Review
- Transcriptional regulatory network analysis uncovers modular gene control and potential key regulators in diabetic cardiomyopathy.Frontiers in cell and developmental biology · 2026Article
- Endosomal Mechanisms in Heart Failure Pathophysiology.Current heart failure reports · 2025Review
- The Impact of PCSK9 on Diabetic Cardiomyopathy: Mechanisms and Implications.Biomolecules · 2025Review
- Ferroptosis: a potential therapeutic target in cardio-cerebrovascular diseases.Molecular and cellular biochemistry · 2025Review
- Chemical Food Safety in Europe Under the Spotlight: Principles, Regulatory Framework and Roadmap for Future Directions.Foods (Basel, Switzerland) · 2025Review
- Effect of high glucose on the gene expression profiling in cardiac fibroblasts from rats at different ages.PeerJ · 2025Article
- Article
- The role of protein S-acylation in vascular injury associated with metabolic disorders.Frontiers in endocrinology · 2025Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperglycemia activates toll-like receptor 4 (TLR4) to induce inflammation in diabetic cardiomyopathy (DCM). However, the mechanisms of TLR4 activation remain unclear. Here we examine the role of myeloid differentiation 2 (MD2), a co-receptor of TLR4, in high glucose (HG)- and diabetes-induced inflammatory cardiomyopathy. We show increased MD2 in heart tissues of diabetic mice and serum of human diabetic subjects. MD2 deficiency in mice inhibits TLR4 pathway activation, which correlates with reduced myocardial remodeling and improved cardiac function. Mechanistically, we show that HG induces extracellular advanced glycation end products (AGEs), which bind directly to MD2, leading to formation of AGEs-MD2-TLR4 complex and initiation of pro-inflammatory pathways. We further detect elevated AGE-MD2 complexes in heart tissues and serum of diabetic mice and human subjects with DCM. In summary, we uncover a new mechanism of HG-induced inflammatory responses and myocardial injury, in which AGE products directly bind MD2 to drive inflammatory DCM.
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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.