ArticleExperimental & molecular medicine2021
Regulation of MDM2 E3 ligase-dependent vascular calcification by MSX1/2.
Article in Experimental & molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Vascular calcification: pathogenic mechanisms, signaling crosstalk and translational therapeutics.Signal transduction and targeted therapy · 2026Review
- YAK577 Attenuates Vascular Calcification by Targeting an MMP14-NOX2/ROS Axis in VSMCs and a Vitamin DAntioxidants (Basel, Switzerland) · 2026Article
- [Advances in Animal Modeling in the Study of Bone-Vascular Axis Comorbidities].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Review
- CBL-b E3 ligase-mediated neddylation and activation of PARP-1 induce vascular calcification.Experimental & molecular medicine · 2024Article
- Placental Tissue Calcification and Its Molecular Pathways in Female Patients with Late-Onset Preeclampsia.Biomolecules · 2024Article
- Association of serum calcium levels with diabetic kidney disease in normocalcemic type 2 diabetes patients: a cross-sectional study.Scientific reports · 2024Article
- TXNIP Suppresses the Osteochondrogenic Switch of Vascular Smooth Muscle Cells in Atherosclerosis.Circulation research · 2023Article
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular calcification increases morbidity and mortality in patients with cardiovascular and renal diseases. Previously, we reported that histone deacetylase 1 prevents vascular calcification, whereas its E3 ligase, mouse double minute 2 homolog (MDM2), induces vascular calcification. In the present study, we identified the upstream regulator of MDM2. By utilizing cellular models and transgenic mice, we confirmed that E3 ligase activity is required for vascular calcification. By promoter analysis, we found that both msh homeobox 1 (Msx1) and msh homeobox 2 (Msx2) bound to the MDM2 promoter region, which resulted in transcriptional activation of MDM2. The expression levels of both Msx1 and Msx2 were increased in mouse models of vascular calcification and in calcified human coronary arteries. Msx1 and Msx2 potentiated vascular calcification in cellular and mouse models in an MDM2-dependent manner. Our results establish a novel role for MSX1/MSX2 in the transcriptional activation of MDM2 and the resultant increase in MDM2 E3 ligase activity during vascular calcification.
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