ArticleThe Journal of clinical investigation2021
ALKBH1-demethylated DNA N6-methyladenine modification triggers vascular calcification via osteogenic reprogramming in chronic kidney disease.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 82 citations in OpenAlex.
- Perirenal fat β₃-adrenergic signaling alleviates renal fibrosis via regulating Bcat2/BCAA-TNFα pathway in diabetic kidney disease.Nature communications · 2026Article
- Serum Acrolein and Peripheral Arterial Stiffness in Non-Dialysis Chronic Kidney Disease: A Cross-Sectional Study.Toxins · 2026Article
- The mechanism of m6A modification in cardiovascular diseases: A systematic review.Genes & diseases · 2026Review
- Blood metabolites mediate causal inference studies on the effect of gut microbiota on the risk of vascular calcification.Journal of advanced research · 2026Article
- Mechanisms of vascular calcification: cellular phenotype switching drives matrix remodeling and mineralized microenvironment formation.Frontiers in cardiovascular medicine · 2026Review
- The methyltransferase N6amt1 regulates hippocampal neurogenesis through 6 mA modification of Txnrd3 DNA.Cellular and molecular life sciences : CMLS · 2025Article
- Medial arterial calcification in ageing and disease: current evidence and knowledge gaps.European heart journal · 2025Review
- Mechanosensor Piezo1‑mediated smooth muscular cell pyroptosis contributes to vascular calcification.International journal of molecular medicine · 2025Article
- Arsenic regulates ALKBH1 abundance and substrate specificity to promote translation and tumorigenicity.Cell reports · 2025Article
- Inhibition of long interspersed nuclear element-1 by nucleoside reverse transcriptase inhibitors attenuates vascular calcification.Signal transduction and targeted therapy · 2025Article
- NEXN protects against vascular calcification by promoting SERCA2 SUMOylation and stabilization.Nature communications · 2025Article
- DNMT3B aggravated renal fibrosis in diabetic kidney disease via activating Wnt/β-catenin signaling pathway.Scientific reports · 2025Article
- N6-Methyladenosine Modification of the Three Components "Writers", "Erasers", and "Readers" in Relation to Osteogenesis.International journal of molecular sciences · 2025Review
- GLS1-Mediated Redundancy in Glutamate Accelerates Arterial Calcification via Activating NMDAR/CaAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- From bone marrow mesenchymal stem cells to diseases: the crucial role of mStem cell research & therapy · 2025Review
- TET2 suppresses vascular calcification by forming an inhibitory complex with HDAC1/2 and SNIP1 independent of demethylation.The Journal of clinical investigation · 2025Article
- Review
- METTL3 obstructs vascular smooth muscle cells osteogenic reprogramming by methylating Runx2 in chronic kidney disease.Communications biology · 2025Article
- Hypermethylation and suppression of microRNA219a-2 activates the ALDH1L2/GSH/PAI-1 pathway for fibronectin degradation in renal fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Regulation of osteogenic differentiation in vascular smooth muscle cells under high-glucose condition.Frontiers in endocrinology · 2025Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular calcification (VC) predicts cardiovascular morbidity and mortality in chronic kidney disease (CKD). To date, the underlying mechanisms remain unclear. We detected leukocyte DNA N6-methyladenine (6mA) levels in patients with CKD with or without aortic arch calcification. We used arteries from CKD mice infected with vascular smooth muscle cell-targeted (VSMC-targeted) adeno-associated virus encoding alkB homolog 1 (Alkbh1) gene or Alkbh1 shRNA to evaluate features of calcification. We identified that leukocyte 6mA levels were significantly reduced as the severity of VC increased in patients with CKD. Decreased 6mA demethylation resulted from the upregulation of ALKBH1. Here, ALKBH1 overexpression aggravated whereas its depletion blunted VC progression and osteogenic reprogramming in vivo and in vitro. Mechanistically, ALKBH1-demethylated DNA 6mA modification could facilitate the binding of octamer-binding transcription factor 4 (Oct4) to bone morphogenetic protein 2 (BMP2) promoter and activate BMP2 transcription. This resulted in osteogenic reprogramming of VSMCs and subsequent VC progression. Either BMP2 or Oct4 depletion alleviated the procalcifying effects of ALKBH1. This suggests that targeting ALKBH1 might be a therapeutic method to reduce the burden of VC in CKD.
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