ArticleJournal of the American Society of Nephrology : JASN2016
Endothelial Krüppel-Like Factor 4 Mediates the Protective Effect of Statins against Ischemic AKI.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 57 citations in OpenAlex.
- The endothelium response to kidney injury.Nature reviews. Nephrology · 2026Review
- KLF4 overexpression protects against complementmediated endothelial injury in transplant-associated thrombotic microangiopathy.Haematologica · 2026Article
- The Mechanism of KLF4-Mediated NF-κB/NLRP3 Pathway Regulating Arteriovenous Fistula Dysfunction.Acta Cardiologica Sinica · 2026Article
- Statins as Modulators of Epithelial to Mesenchymal Transition in Cardiovascular-Kidney-Metabolic Syndrome: a Comprehensive Review of Mechanisms and Therapeutic Implications.Current atherosclerosis reports · 2025Review
- Circular RNA Cdr1as Modulates Macrophage-Mediated Cardiac Reparative Function.Circulation research · 2025Article
- Statins and adhesion molecules: a review of a novel pleiotropic property of statins.Immunologic research · 2025Review
- Cell cycle disorders in podocytes: an emerging and increasingly recognized phenomenon.Cell death discovery · 2025Review
- An endothelial SOX18-mevalonate pathway axis enables repurposing of statins for infantile hemangioma.The Journal of clinical investigation · 2025Article
- The KLF4/Galectin-3 cascade is a key determinant of tubular cell death and acute kidney injury.International journal of biological sciences · 2025Article
- The pleiotropic effects of statins: a comprehensive exploration of neurovascular unit modulation and blood-brain barrier protection.Molecular medicine (Cambridge, Mass.) · 2024Review
- Exploring the Functionality of the Krüppel-like Factors in Kidney Development, Metabolism, and Diseases.Life (Basel, Switzerland) · 2024Review
- Ultrasound molecular imaging for early detection of acute renal ischemia-reperfusion injury.Bioengineering & translational medicine · 2024Article
- Participation of Krüppel-like Factors in Atherogenesis.Metabolites · 2023Review
- Altered DNA methylation in kidney disease: useful markers and therapeutic targets.Clinical and experimental nephrology · 2022Review
- Atorvastatin Decreases Renal Calcium Oxalate Stone Deposits by Enhancing Renal Osteopontin Expression in Hyperoxaluric Stone-Forming Rats Fed a High-Fat Diet.International journal of molecular sciences · 2022Article
- Sirtuin 7 Deficiency Reduces Inflammation and Tubular Damage Induced by an Episode of Acute Kidney Injury.International journal of molecular sciences · 2022Article
- Renoprotective Effect of KLF2 on Glomerular Endothelial Dysfunction in Hypertensive Nephropathy.Cells · 2022Article
- Phenotypic diversity and metabolic specialization of renal endothelial cells.Nature reviews. Nephrology · 2021Review
- Expressions and related mechanisms of miR-212 and KLF4 in rats with acute kidney injury.Molecular and cellular biochemistry · 2021Article
- KLF4 initiates sustained YAP activation to promote renal fibrosis in mice after ischemia-reperfusion kidney injury.Acta pharmacologica Sinica · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial cells participate in the pathophysiology of ischemic AKI by increasing the expression of cell adhesion molecules and by recruiting inflammatory cells. We previously showed that endothelial Krüppel-like factor 4 (Klf4) regulates vascular cell adhesion molecule 1 (Vcam1) expression and neointimal formation after carotid injury. In this study, we determined whether endothelial Klf4 is involved in ischemic AKI using endothelial Klf4 conditional knockout (Klf4 cKO) mice generated by breeding Tek-Cre mice and Klf4 floxed mice. Klf4 cKO mice were phenotypically normal before surgery. However, after renal ischemia-reperfusion injury, Klf4 cKO mice exhibited elevated serum levels of urea nitrogen and creatinine and aggravated renal histology compared with those of Klf4 floxed controls. Moreover, Klf4 cKO mice exhibited enhanced accumulation of neutrophils and lymphocytes and elevated expression of cell adhesion molecules, including Vcam1 and Icam1, in injured kidneys. Notably, statins ameliorated renal ischemia-reperfusion injury in control mice but not in Klf4 cKO mice. Mechanistic analyses in cultured endothelial cells revealed that statins increased KLF4 expression and that KLF4 mediated the suppressive effect of statins on TNF-α-induced VCAM1 expression by reducing NF-κB binding to the VCAM1 promoter. These results provide evidence that endothelial Klf4 is renoprotective and mediates statin-induced protection against ischemic AKI by regulating the expression of cell adhesion molecules and concomitant recruitment of inflammatory cells.
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