ArticleCell & bioscience2023
Loss of TET2 impairs endothelial angiogenesis via downregulating STAT3 target genes.
Article in Cell & bioscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 30 citations in OpenAlex.
- Clonal Hematopoiesis in Colorectal Cancer: Mechanisms and Implications.Cancer medicine · 2026Review
- DNA/RNA Methylation-Driven Coronary Microvascular Dysfunction: Emerging Pathogenic Mechanisms and Therapeutic Opportunities for Heart Failure in Diabetes.Cardiovascular drugs and therapy · 2026Review
- Targeting Epigenetics in Ischemic Stroke: From Mechanisms to Therapeutics.Current neuropharmacology · 2026Review
- TET2 has endothelial-specific roles in interferon responses that are dysregulated by hyperglycemia in vitro and in vivo.The Journal of biological chemistry · 2025Article
- DNA dioxygenase TET2 deficiency aggravates sepsis-induced acute lung injury by targeting ITGA10 via the PI3K/AKT signaling pathway.Cellular & molecular biology letters · 2025Article
- PHAX enhanced LIN28B-mediated PBX3 mRNA stability to promote esophageal cancer development.Cancer science · 2025Article
- Article
- Histone lactylation-derived TET2 enhanced Arg1-mediated MDSC immunosuppression.Frontiers in immunology · 2025Article
- Research progress on DNA hydroxymethylation in atrial fibrillation: a review.Frontiers in pharmacology · 2025Review
- Unravelling the role of TET2 in venous thromboembolism: insights into mechanisms and therapeutic implications.Frontiers in cardiovascular medicine · 2025Review
- Vasculogenic skin reprogramming requires TET-mediated gene demethylation in fibroblasts for rescuing impaired perfusion in diabetes.Nature communications · 2024Article
- Endothelial TET2 regulates the white adipose browning and metabolism via fatty acid oxidation in obesity.Redox biology · 2024Article
- Hypoxia-induced P4HA1 overexpression promotes post-ischemic angiogenesis by enhancing endothelial glycolysis through downregulating FBP1.Journal of translational medicine · 2024Article
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Authors and funding
12 authors at 2 institutions in 1 country.
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Abstract
backgroundIschemic diseases represent a major global health care burden. Angiogenesis is critical in recovery of blood flow and repair of injured tissue in ischemic diseases. Ten-eleven translocation protein 2 (TET2), a member of DNA demethylases, is involved in many pathological processes. However, the role of TET2 in angiogenesis is still unrevealed.
methodsTET2 was screened out from three DNA demethylases involved in 5-hydroxylmethylcytosine (5-hmC) regulation, including TET1, TET2 and TET3. Knockdown by small interfering RNAs and overexpression by adenovirus were used to evaluate the role of TET2 on the function of endothelial cells. The blood flow recovery and density of capillary were analyzed in the endothelial cells-specific TET2-deficient mice. RNA sequencing was used to identify the TET2-mediated mechanisms under hypoxia. Co-immunoprecipitation (Co-IP), chromatin immunoprecipitation-qPCR (ChIP-qPCR) and glucosylated hydroxymethyl-sensitive-qPCR (GluMS-qPCR) were further performed to reveal the interaction of TET2 and STAT3.
resultsTET2 was significantly downregulated in endothelial cells under hypoxia and led to a global decrease of 5-hmC level. TET2 knockdown aggravated the hypoxia-induced dysfunction of endothelial cells, while TET2 overexpression alleviated the hypoxia-induced dysfunction. Meanwhile, the deficiency of TET2 in endothelial cells impaired blood flow recovery and the density of capillary in the mouse model of hindlimb ischemia. Mechanistically, RNA sequencing indicated that the STAT3 signaling pathway was significantly inhibited by TET2 knockdown. Additionally, Co-IP, ChIP-qPCR and GluMS-qPCR further illustrated that STAT3 recruited and physically interacted with TET2 to activate STAT3 target genes. As expected, the effects of TET2 overexpression were completely suppressed by STAT3 silencing in vitro.
conclusionsOur study suggests that the deficiency of TET2 in endothelial cells impairs angiogenesis via suppression of the STAT3 signaling pathway. These findings give solid evidence for TET2 to be a therapeutic alternative for ischemic diseases.
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