ArticleThe Journal of clinical investigation2022
SIRT6 protects vascular smooth muscle cells from osteogenic transdifferentiation via Runx2 in chronic kidney disease.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed.
- Review
- Deep learning-based automated segmentation and quantification of aortic arch calcification at chest radiograph.BMC geriatrics · 2026Article
- Sirt3 Genetically Engineered Apoptotic Bodies Alleviate Skeletal Aging by Limiting Aggravated NLRP3 Inflammasome Activation of Senescent Macrophages.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Epigenetic Regulation and Molecular Mechanisms in Cardiovascular Diseases: A Review of Recent Advances and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Runx2 acetylation enhances pulmonary inflammation in chronic obstructive pulmonary disease through activating CDK8.Respiratory research · 2026Article
- Integrative omics and experimental validation reveal METTL17 and SLC27A1 as biomarkers and potential therapeutic targets in chronic kidney disease.Frontiers in immunology · 2026Article
- Mechanisms of vascular calcification: cellular phenotype switching drives matrix remodeling and mineralized microenvironment formation.Frontiers in cardiovascular medicine · 2026Review
- STUB1 stabilizes sirtuin 6 via K63-linked ubiquitination to promote NRF2 deacetylation for enhanced ferroptosis resistance after spinal cord injury.Burns & trauma · 2026Article
- Vascular Smooth Muscle Cell-Specific BCAT2 Deficiency Attenuates Diabetic Atherosclerotic Calcification via Histone Propionylation.Research (Washington, D.C.) · 2026Article
- Review
- Niacin inhibits vascular calcification via modulating of SIRT1/SIRT6 signaling pathway.Cell death discovery · 2025Article
- La Ribonucleoprotein 7 Protects Vascular Smooth Muscle Cell Contractile Phenotype in CKD by Coupling with P300.Journal of the American Society of Nephrology : JASN · 2025Article
- Medial arterial calcification in ageing and disease: current evidence and knowledge gaps.European heart journal · 2025Review
- SIRT6 Lysine-Demyristoylates ATF2 to Ameliorate Vascular Injury via PRKCD/VE-Cadherin Pathway Regulating Vascular Endothelial Barrier.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Vascular Calcification and CKD: Challenges, Emerging Targets, and Future Perspectives.Clinical journal of the American Society of Nephrology : CJASN · 2025Article
- The Mechanism and Potential Therapeutic Strategies of Vascular Aging.Aging medicine (Milton (N.S.W)) · 2025Review
- Cellular senescence in kidney diseases.Chinese medical journal · 2025Review
- Long-Term In Vivo Administration of Panaxynol Alleviates Diabetes-Induced Vascular Calcification by Modulating Sirt6-Mediated sEH Function in Perivascular Adipose Tissue.Journal of agricultural and food chemistry · 2025Article
- Knockdown of RGMa reduces vascular calcification by inhibiting the AKT signaling pathway.Scientific reports · 2025Article
- miR-769-5p has diagnostic value in acute kidney injury in intensive care unit patients and mediates disease development by targeting SIRT6.BMC nephrology · 2025Article
23 more citing papers are in PubMed but not listed here.
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11 authors.
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Abstract
Vascular calcification (VC) is regarded as an important pathological change lacking effective treatment and associated with high mortality. Sirtuin 6 (SIRT6) is a member of the Sirtuin family, a class III histone deacetylase and a key epigenetic regulator. SIRT6 has a protective role in patients with chronic kidney disease (CKD). However, the exact role and molecular mechanism of SIRT6 in VC in patients with CKD remain unclear. Here, we demonstrated that SIRT6 was markedly downregulated in peripheral blood mononuclear cells (PBMCs) and in the radial artery tissue of patients with CKD with VC. SIRT6-transgenic (SIRT6-Tg) mice showed alleviated VC, while vascular smooth muscle cell-specific (VSMC-specific) SIRT6 knocked-down mice showed severe VC in CKD. SIRT6 suppressed the osteogenic transdifferentiation of VSMCs via regulation of runt-related transcription factor 2 (Runx2). Coimmunoprecipitation (co-IP) and immunoprecipitation (IP) assays confirmed that SIRT6 bound to Runx2. Moreover, Runx2 was deacetylated by SIRT6 and further promoted nuclear export via exportin 1 (XPO1), which in turn caused degradation of Runx2 through the ubiquitin-proteasome system. These results demonstrated that SIRT6 prevented VC by suppressing the osteogenic transdifferentiation of VSMCs, and as such targeting SIRT6 may be an appealing therapeutic target for VC in CKD.
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