ArticleThe Journal of biological chemistry2009
Hyperglycemia regulates RUNX2 activation and cellular wound healing through the aldose reductase polyol pathway.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Intensive versus conventional glycaemic control for treating diabetic foot ulcers.The Cochrane database of systematic reviews · 2016Pooled it
- Advances in Chinese herbal medicine for diabetic wound treatment: from tradition to innovation.Chinese medicine · 2026Review
- Review
- Role of oxidative stress in impaired type II diabetic bone repair: scope for antioxidant therapy intervention?Frontiers in dental medicine · 2024Review
- Modulatory effect of caffeic acid in alleviating diabetes and associated complications.World journal of diabetes · 2023Review
- Probable Treatment Targets for Diabetic Retinopathy Based on an Integrated Proteomic and Genomic Analysis.Translational vision science & technology · 2023Article
- Potential role of oxidative stress in the pathogenesis of diabetic bladder dysfunction.Nature reviews. Urology · 2022Review
- MALAT1 sponges miR-26a and miR-26b to regulate endothelial cell angiogenesis via PFKFB3-driven glycolysis in early-onset preeclampsia.Molecular therapy. Nucleic acids · 2021Article
- A novel phosphorylation by AMP-activated kinase regulates RUNX2 from ubiquitination in osteogenesis over adipogenesis.Cell death & disease · 2018Article
- Characterization of CADD522, a small molecule that inhibits RUNX2-DNA binding and exhibits antitumor activity.Oncotarget · 2017Article
- Palmitic acid dysregulates the Hippo-YAP pathway and inhibits angiogenesis by inducing mitochondrial damage and activating the cytosolic DNA sensor cGAS-STING-IRF3 signaling mechanism.The Journal of biological chemistry · 2017Article
- Article
- The RUNX2 Transcription Factor Negatively Regulates SIRT6 Expression to Alter Glucose Metabolism in Breast Cancer Cells.Journal of cellular biochemistry · 2015Article
- Inpatient HbA1c testing: a prospective observational study.BMJ open diabetes research & care · 2015Article
- Application of VEGFA and FGF-9 enhances angiogenesis, osteogenesis and bone remodeling in type 2 diabetic long bone regeneration.PloS one · 2015Article
- Hyperglycemia and redox status regulate RUNX2 DNA-binding and an angiogenic phenotype in endothelial cells.Microvascular research · 2015Article
- Runx2 activates PI3K/Akt signaling via mTORC2 regulation in invasive breast cancer cells.Breast cancer research : BCR · 2014Article
- A quantitative assay to study protein:DNA interactions, discover transcriptional regulators of gene expression, and identify novel anti-tumor agents.Journal of visualized experiments : JoVE · 2013Article
- NEU1 and NEU3 sialidase activity expressed in human lung microvascular endothelia: NEU1 restrains endothelial cell migration, whereas NEU3 does not.The Journal of biological chemistry · 2012Article
- Glucose-activated RUNX2 phosphorylation promotes endothelial cell proliferation and an angiogenic phenotype.Journal of cellular biochemistry · 2012Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Diabetes mellitus accelerates cardiovascular microangiopathies and atherosclerosis, which are a consequence of hyperglycemia. The aldose reductase (AR) polyol pathway contributes to these microvascular complications, but how it mediates vascular damage in response to hyperglycemia is less understood. The RUNX2 transcription factor, which is repressed in diabetic animals, promotes vascular endothelial cell (EC) migration, proliferation, and angiogenesis. Here we show that physiological levels of glucose (euglycemia) increase RUNX2 DNA binding and transcriptional activity, whereas hyperglycemia does not. However, inhibition of AR reverses hyperglycemic suppression of RUNX2. IGF-1 secretion and IGF receptor phosphorylation by autocrine IGF-1 occur equally in euglycemic or hyperglycemic conditions, suggesting that reduced RUNX2 activity in response to hyperglycemia is not because of altered IGF-1/IGF receptor activation. AR also negatively regulates RUNX2-dependent vascular remodeling in an EC wounded monolayer assay, which is reversed by specific AR inhibition in hyperglycemia. Thus, euglycemia supports RUNX2 activity and promotes normal microvascular EC migration and wound healing, which are repressed under hyperglycemic conditions through the AR polyol pathway.
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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.