ArticleThe Journal of biological chemistry2019
Hyperglycemia induces vascular smooth muscle cell dedifferentiation by suppressing insulin receptor substrate-1-mediated p53/KLF4 complex stabilization.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Histone modification of endothelial-mesenchymal transition in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Pooled it
- Recent advances and emerging perspectives in vascular and cardiovascular research: A 2025 update.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Review on the Relationship Between TyG Index and CVD Incidence in Patients With T2DM With NAFLD.International journal of endocrinology · 2026Review
- Association of TyG with Survival and Metabolic Alterations in Severe Fever with Thrombocytopenia Syndrome: A Single- Centre Retrospective Study.Infection and drug resistance · 2026Article
- Gene expression profiling of KLF4 and KLF5 in visceral adipose tissue of obese women: insights into adipogenic and metabolic regulation.Lipids in health and disease · 2025Article
- Review
- Silicified curcumin microspheres Combats cardiovascular diseases via Nrf2/HO-1 pathway.Bioactive materials · 2025Article
- The mediating role of the TyG index in the relationship between circadian syndrome and cancer among middle-aged and elderly Chinese.BMC cancer · 2025Article
- The Emerging Role of p21 in Diabetes and Related Metabolic Disorders.International journal of molecular sciences · 2024Review
- Integrative analysis of gene expression, protein abundance, and metabolomic profiling elucidates complex relationships in chronic hyperglycemia-induced changes in human aortic smooth muscle cells.Journal of biological engineering · 2024Article
- Dynamin-related protein 1 mediates the therapeutic effect of isoliquiritigenin in diabetic intimal hyperplasia via regulation of mitochondrial fission.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- The role of miR-143/miR-145 in the development, diagnosis, and treatment of diabetes.Journal of diabetes and metabolic disorders · 2024Review
- High glucose promotes atherosclerosis by regulating miRNA let7d-5p level.Journal of diabetes investigation · 2024Article
- Emirates consensus recommendations on cardiovascular risk management in type 2 diabetes.Frontiers in endocrinology · 2024Review
- The inverse association between DNA gaps and HbA1c levels in type 2 diabetes mellitus.Scientific reports · 2023Article
- Decreased Alu methylation in type 2 diabetes mellitus patients increases HbA1c levels.Journal of clinical laboratory analysis · 2023Article
- Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Article
- Protection of diabetes in aortic abdominal aneurysm: Are antidiabetics the real effectors?Frontiers in cardiovascular medicine · 2023Review
- A novel 6-metabolite signature for prediction of clinical outcomes in type 2 diabetic patients undergoing percutaneous coronary intervention.Cardiovascular diabetology · 2022Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Hyperglycemia and insulin resistance accelerate atherosclerosis by an unclear mechanism. The two factors down-regulate insulin receptor substrate-1 (IRS-1), an intermediary of the insulin/IGF-I signaling system. We previously reported that IRS-1 down-regulation leads to vascular smooth muscle cell (VSMC) dedifferentiation and that IRS-1 deletion from VSMCs in normoglycemic mice replicates this response. However, we did not determine IRS-1's role in mediating differentiation. Here, we sought to define the mechanism by which IRS-1 maintains VSMC differentiation. High glucose or IRS-1 knockdown decreased p53 levels by enhancing MDM2 proto-oncogene (MDM2)-mediated ubiquitination, resulting in decreased binding of p53 to Krüppel-like factor 4 (KLF4). Exposure to nutlin-3, which dissociates MDM2/p53, decreased p53 ubiquitination and enhanced the p53/KLF4 association and differentiation marker protein expression. IRS-1 overexpression in high glucose inhibited the MDM2/p53 association, leading to increased p53 and p53/KLF4 levels, thereby increasing differentiation. Nutlin-3 treatment of diabetic or
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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.