ArticleThe Journal of biological chemistry2011
down-regulation of Kruppel-like factor-4 (KLF4) by microRNA-143/145 is critical for modulation of vascular smooth muscle cell phenotype by transforming growth factor-beta and bone morphogenetic protein 4.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
146 citing papers in PubMed, 238 citations in OpenAlex.
- ChemR23 prevents phenotypic switching of vascular smooth muscle cells into macrophage-like foam cells in atherosclerosis.Cardiovascular research · 2026Article
- Epigenetic Mechanisms in Heart Diseases.Reviews in cardiovascular medicine · 2025Review
- Recent progress in exosomal non-coding RNAs research related to idiopathic pulmonary fibrosis.Frontiers in genetics · 2025Review
- Article
- MicroRNA-mediated Krüppel-like factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4'-methylene diphenyl diisocyanate exposed macrophages.Xenobiotica; the fate of foreign compounds in biological systems · 2024Article
- Small nucleolar RNA host gene 18 controls vascular smooth muscle cell contractile phenotype and neointimal hyperplasia.Cardiovascular research · 2024Article
- Defining the Role of the miR-145-KLF4-αSMA Axis in Mitral Valvular Interstitial Cell Activation in Myxomatous Mitral Valve Prolapse Using the Canine Model.International journal of molecular sciences · 2024Article
- Roles of Vascular Smooth Muscle Cells in Atherosclerotic Calcification.Journal of lipid and atherosclerosis · 2023Article
- Evaluation of Arterial Histopathology and microRNA Expression That Underlie Ultrasonography Findings in Temporal Arteries of Patients with Giant Cell Arteritis.International journal of molecular sciences · 2023Article
- How vascular smooth muscle cell phenotype switching contributes to vascular disease.Cell communication and signaling : CCS · 2022Review
- Functions of the bone morphogenetic protein signaling pathway through non-coding RNAs.Non-coding RNA research · 2022Review
- Curcumin attenuates vascular calcification via the exosomal miR-92b-3p/KLF4 axis.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- MiR-3571 modulates the proliferation and migration of vascular smooth muscle cells by targeting claudin 1.International journal of medical sciences · 2022Article
- Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis.Nature communications · 2021Article
- Article
- Mesenchymal Stem Cells Alter MicroRNA Expression and Attenuate Thoracic Aortic Aneurysm Formation.The Journal of surgical research · 2021Article
- Six Shades of Vascular Smooth Muscle Cells Illuminated by KLF4 (Krüppel-Like Factor 4).Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Vascular smooth muscle cells in atherosclerosis: time for a re-assessment.Cardiovascular research · 2021Review
- Generation and Characterization of Human Mesenchymal Stem Cell-Derived Smooth Muscle Cells.International journal of molecular sciences · 2021Article
- MRTF: Basic Biology and Role in Kidney Disease.International journal of molecular sciences · 2021Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
In the postnatal vasculature, fully differentiated and quiescent vascular smooth muscle cells (VSMCs) in a "contractile" phenotype are required for the normal regulation of vascular tone. The transforming growth factor-β (TGF-β) superfamily of growth factors (TGF-βs and bone morphogenetic proteins (BMPs)) are potent inducers of contractile phenotype and mediate (i) induction of contractile genes, and (ii) inhibition of VSMC growth and migration. Transcription of contractile genes is positively regulated by a regulatory DNA element called a CArG box. The CArG box is activated by the binding of serum response factor and its coactivators, myocardin (Myocd) or Myocd-related transcription factors (MRTFs). Krüppel-like factor-4 (KLF4) is known to inhibit activation of the CArG box. However, the potential role of KLF4 in the contractile activities of TGF-β or BMP has not been explored. Here, we demonstrate that TGF-β and BMP4 rapidly down-regulate KLF4 through induction of microRNA-143 (miR-143) and miR-145, which leads to a reduction of KLF4 transcripts and decreased KLF4 protein expression. Inhibition of miR-145 prevents down-regulation of KLF4 and activation of contractile genes by TGF-β or BMP4, suggesting that modulation of KLF4 is a prerequisite for induction of contractile genes by TGF-β and BMP4. Interestingly, both TGF-β and BMP4 activate transcription of the miR-143/145 gene cluster through the CArG box, however, TGF-β mediates this effect through induction of Myocd expression, whereas BMP4 utilizes nuclear translocation of MRTF-A. Thus, this study sheds light on both the similarities and the differences of TGF-β and BMP4 signaling in the regulation of KLF4 and contractile genes.
Indexed as
Identifiers
What OpenQuestion holds
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.