ArticleThe Journal of pharmacology and experimental therapeutics2010
Cyclosporine up-regulates Krüppel-like factor-4 (KLF4) in vascular smooth muscle cells and drives phenotypic modulation in vivo.
Article in The Journal of pharmacology and experimental therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- Non-canonical ceRNA-independent mechanism of the lncRNA-H19/miR-212-5p axis targeting KLF4 in Hcy-triggered VSMCs dysfunction and atherogenesis.Scientific reports · 2026Article
- Diverse effects of calcineurin in vascular smooth muscle cells: physiological activators and the controversial actions of clinical inhibitors.Frontiers in pharmacology · 2026Review
- Role of Carvedilol in Inhibiting the Proliferation and Migration of Vascular Smooth Muscle Cells by Upregulating microRNA-145 Expression.Physiological research · 2025Article
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- Basal ATP release signals through the P2YAtherosclerosis · 2024Article
- Down-regulation of the Smad signaling by circZBTB46 via the Smad2-PDLIM5 axis to inhibit type I collagen expression.Journal of geriatric cardiology : JGC · 2023Article
- A cost-effective machine learning-based method for preeclampsia risk assessment and driver genes discovery.Cell & bioscience · 2023Article
- The mechanism and therapy of aortic aneurysms.Signal transduction and targeted therapy · 2023Review
- Elevated circulating Krüppel-like factor 4 level as a novel independent marker of the proatherogenic risk in patients with psoriasis: a preliminary study.Postepy dermatologii i alergologii · 2021Article
- Six Shades of Vascular Smooth Muscle Cells Illuminated by KLF4 (Krüppel-Like Factor 4).Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- miR-484 suppresses endocrine therapy-resistant cells by inhibiting KLF4-induced cancer stem cells in estrogen receptor-positive cancers.Breast cancer (Tokyo, Japan) · 2021Article
- RhoA/ROCK Pathway Activation is Regulated by AT1 Receptor and Participates in Smooth Muscle Migration and Dedifferentiation via Promoting Actin Cytoskeleton Polymerization.International journal of molecular sciences · 2020Article
- miR-182-3p/Myadm contribute to pulmonary artery hypertension vascular remodeling via a KLF4/p21-dependent mechanism.Theranostics · 2020Article
- MicroRNA-92 regulates vascular smooth muscle cell function by targeting KLF4 during vascular restenosis and injury.International journal of clinical and experimental pathology · 2019Article
- Krüppel-Like Factors in Vascular Inflammation: Mechanistic Insights and Therapeutic Potential.Frontiers in cardiovascular medicine · 2018Review
- Upregulation of distinct collagen transcripts in post-surgery scar tissue: a study of conjunctival fibrosis.Disease models & mechanisms · 2017Article
- Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation.The Journal of biological chemistry · 2017Article
- Regulation of vascular smooth muscle phenotype by cross-regulation of krüppel-like factors.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2017Article
- Endothelial Transdifferentiation of Tumor Cells Triggered by the Twist1-Jagged1-KLF4 Axis: Relationship between Cancer Stemness and Angiogenesis.Stem cells international · 2016Review
- The Janus-faced roles of Krüppel-like factor 4 in oral squamous cell carcinoma cells.Oncotarget · 2015Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cyclosporine A (CSA, calcineurin inhibitor) has been shown to block both vascular smooth muscle cell (VSMC) proliferation in cell culture and vessel neointimal formation following injury in vivo. The purpose of this study was to determine molecular and pathological effects of CSA on VSMCs. Using real-time reverse transcription-polymerase chain reaction, Western blot analysis, and immunofluorescence microscopy, we show that CSA up-regulated the expression of Krüppel-like factor-4 (KLF4) in VSMCs. KLF4 plays a key role in regulating VSMC phenotypic modulation. KLF4 antagonizes proliferation, facilitates migration, and down-regulates VSMC differentiation marker gene expression. We show that the VSMC differentiation marker genes smooth muscle alpha-actin (ACTA2), transgelin (TAGLN), smoothelin (SMTN), and myocardin (MYOCD) are all down-regulated by CSA in VSMC monoculture, whereas cyclin-dependent kinase inhibitor-1A (CDKN1A) and matrix metalloproteinase-3 (MMP3) are up-regulated. CSA did not affect the abundance of the VSMC microRNA (MIR) markers MIR143 and MIR145. Administration of CSA to rat carotid artery in vivo resulted in acute and transient suppression of ACTA2, TAGLN, SMTN, MYOCD, and smooth muscle myosin heavy chain (MYH11) mRNA levels. The tumor suppressor genes KLF4, p53, and CDKN1A, however, were up-regulated, as well as MMP3, MMP9, and collagen-VIII. CSA-treated arteries showed remarkable remodeling, including breakdown of the internal elastic lamina and reorientation of VSMCs, as well as increased KLF4 immunostaining in VSMCs and endothelial cells. Altogether, these data show that cyclosporin up-regulates KLF4 expression and promotes phenotypic modulation of VSMCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.