ArticleActa pharmacologica Sinica2023
Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs.
Article in Acta pharmacologica Sinica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 29 citations in OpenAlex.
- Association between microinflammatory state and cardiac valvular calcification in patients undergoing maintenance hemodialysis: a single-centre observational study.BMC nephrology · 2026Observational
- Decreased concentration of transcription factor 21 in patients with chronic schizophrenia is associated with an increased coronary artery calcium score.BMC psychiatry · 2026Article
- Emerging insights into inflammation-driven atherosclerosis: immune cell mechanisms.Frontiers in cardiovascular medicine · 2026Review
- Endothelial BMP6 Drives Hemodynamic-Dependent VSMCs Calcification in Carotid Atherosclerosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Association of suPAR with progression of cardiovascular calcification and cardiovascular outcomes in peritoneal dialysis patients.Renal failure · 2025Article
- Neuronal Endothelin a Receptor Mediates Experimental and Clinical Vascular Pain through an Endothelial-Neural Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The association between the aggregate index of systemic inflammation and abdominal aortic calcification: a National health and nutrition examination survey.Journal of cardiothoracic surgery · 2025Article
- Single-Cell Transcriptomics Revealed E-Cigarettes-Induced Vascular Remodeling by EnhancingMedComm · 2025Article
- Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/β-catenin signalling pathway.Journal of advanced research · 2025Article
- Associations of Gla-rich protein and interleukin-1β with coronary artery calcification risk in patients with suspected coronary artery disease.Frontiers in endocrinology · 2025Article
- Article
- The role of macrophages in vascular calcification: strategies for diagnosis and treatment.Frontiers in immunology · 2025Review
- Interleukin family in vascular calcification: molecular mechanisms and therapeutic perspectives.Frontiers in cardiovascular medicine · 2025Review
- SOX9 mediates the phenotypic transformation of vascular smooth muscle cells in restenosis after carotid artery injury.Frontiers in cell and developmental biology · 2025Article
- Novel lncRNA LncMSTRG.11341.25 Promotes Osteogenic Differentiation of Human Bone Marrow Stem Cells via the miR-939-5p/PAX8 Axis.Research (Washington, D.C.) · 2025Article
- The serum levels of gasdermin D in uremic patients and its relationship with the prognosis: a prospective observational cohort study.Renal failure · 2024Observational
- Nesfatin-1 enhances vascular smooth muscle calcification through facilitating BMP-2 osteogenic signaling.Cell communication and signaling : CCS · 2024Article
- Vascular Calcification: Molecular Networking, Pathological Implications and Translational Opportunities.Biomolecules · 2024Review
- PCSK9 inhibitors ameliorate arterial stiffness in ACS patients: evidences from Mendelian randomization, a retrospective study and basic experiments.Frontiers in medicine · 2024Article
- Elucidating VSMC phenotypic transition mechanisms to bridge insights into cardiovascular disease implications.Frontiers in cardiovascular medicine · 2024Review
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
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Abstract
Vascular calcification is caused by the deposition of calcium salts in the intimal or tunica media layer of the aorta, which increases the risk of cardiovascular events and all-cause mortality. However, the mechanisms underlying vascular calcification are not fully clarified. Recently it has been shown that transcription factor 21 (TCF21) is highly expressed in human and mouse atherosclerotic plaques. In this study we investigated the role of TCF21 in vascular calcification and the underlying mechanisms. In carotid artery atherosclerotic plaques collected from 6 patients, we found that TCF21 expression was upregulated in calcific areas. We further demonstrated TCF21 expression was increased in an in vitro vascular smooth muscle cell (VSMC) osteogenesis model. TCF21 overexpression promoted osteogenic differentiation of VSMC, whereas TCF21 knockdown in VSMC attenuated the calcification. Similar results were observed in ex vivo mouse thoracic aorta rings. Previous reports showed that TCF21 bound to myocardin (MYOCD) to inhibit the transcriptional activity of serum response factor (SRF)-MYOCD complex. We found that SRF overexpression significantly attenuated TCF21-induced VSMC and aortic ring calcification. Overexpression of SRF, but not MYOCD, reversed TCF21-inhibited expression of contractile genes SMA and SM22. More importantly, under high inorganic phosphate (3 mM) condition, SRF overexpression reduced TCF21-induced expression of calcification-related genes (BMP2 and RUNX2) as well as vascular calcification. Moreover, TCF21 overexpression enhanced IL-6 expression and downstream STAT3 activation to facilitate vascular calcification. Both LPS and STAT3 could induce TCF21 expression, suggesting that the inflammation and TCF21 might form a positive feedback loop to amplify the activation of IL-6/STAT3 signaling pathway. On the other hand, TCF21 induced production of inflammatory cytokines IL-1β and IL-6 in endothelial cells (ECs) to promote VSMC osteogenesis. In EC-specific TCF21 knockout (TCF21
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