ArticleThe Journal of biological chemistry2012
Kruppel-like factor 4 contributes to high phosphate-induced phenotypic switching of vascular smooth muscle cells into osteogenic cells.
Article in The Journal of biological chemistry, 2012. 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, 76 citations in OpenAlex.
- Atherosclerotic Cell Fates: A Single-Cell View of ER Stress.Journal of cardiovascular development and disease · 2026Review
- Exosomes in arteriovenous fistula stenosis.Frontiers in cell and developmental biology · 2025Review
- Regulation of osteogenic differentiation in vascular smooth muscle cells under high-glucose condition.Frontiers in endocrinology · 2025Review
- Phosphonoformic acid reduces hyperphosphatemia-induced vascular calcification via Pit-1.The Journal of international medical research · 2024Article
- Phenotypic Switching of Vascular Smooth Muscle Cells in Atherosclerosis.Journal of the American Heart Association · 2023Review
- FAM3A reshapes VSMC fate specification in abdominal aortic aneurysm by regulating KLF4 ubiquitination.Nature communications · 2023Article
- MicroRNA-145 and microRNA-486 are potential serum biomarkers for vascular calcification.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Article
- Roles of Vascular Smooth Muscle Cells in Atherosclerotic Calcification.Journal of lipid and atherosclerosis · 2023Article
- Insights into the toxicological effects of nanomaterials on atherosclerosis: mechanisms involved and influence factors.Journal of nanobiotechnology · 2023Review
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Inflammatory, Metabolic, and Coagulation Effects on Medial Arterial Calcification in Patients with Peripheral Arterial Disease.International journal of molecular sciences · 2023Review
- Klf4-Sirt3/Pparα-Lcad pathway contributes to high phosphate-induced lipid degradation.Cell communication and signaling : CCS · 2023Article
- Flavocoxid Ameliorates Aortic Calcification Induced by Hypervitaminosis DCardiovascular drugs and therapy · 2022Article
- How vascular smooth muscle cell phenotype switching contributes to vascular disease.Cell communication and signaling : CCS · 2022Review
- Microcalcification and Thoracic Aortopathy: A Window Into Disease Severity.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Curcumin attenuates vascular calcification via the exosomal miR-92b-3p/KLF4 axis.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- Vitamin D Treatment Prevents Uremia-Induced Reductions in Aortic microRNA-145 Attenuating Osteogenic Differentiation despite Hyperphosphatemia.Nutrients · 2022Article
- Long-term efficacy and safety of iron-based phosphate binders, ferric citrate hydrate and sucroferric oxyhydroxide, in hemodialysis patients.International urology and nephrology · 2022Article
- Emerging Concepts of Vascular Cell Clonal Expansion in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2022Review
- Cellular Crosstalk in the Vascular Wall Microenvironment: The Role of Exosomes in Vascular Calcification.Frontiers in cardiovascular medicine · 2022Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperphosphatemia in chronic kidney disease is highly associated with vascular calcification. Previous studies have shown that high phosphate-induced phenotypic switching of vascular smooth muscle cells (SMCs) into osteogenic cells plays an important role in the calcification process. In the present study, we determined whether Krüppel-like factor 4 (Klf4) and phosphorylated Elk-1, transcriptional repressors of SMC differentiation marker genes activated by intimal atherogenic stimuli, contributed to this process. Rat aortic SMCs were cultured in the medium with normal (0.9 mmol/liter) or high (4.5 mmol/liter) phosphate concentration. Results showed that high phosphate concentration induced SMC calcification. Moreover, high phosphate decreased expression of SMC differentiation marker genes including smooth muscle α-actin and SM22α, whereas it increased expression of osteogenic genes, such as Runx2 and osteopontin. High phosphate also induced Klf4 expression, although it did not phosphorylate Elk-1. In response to high phosphate, Klf4 selectively bound to the promoter regions of SMC differentiation marker genes. Of importance, siRNA-mediated knockdown of Klf4 blunted high phosphate-induced suppression of SMC differentiation marker genes, as well as increases in expression of osteogenic genes and calcium deposition. Klf4 was also induced markedly in the calcified aorta of adenine-induced uremic rats. Results provide novel evidence that Klf4 mediates high phosphate-induced conversion of SMCs into osteogenic cells.
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