ArticleAmerican journal of physiology. Heart and circulatory physiology2009
Sp1-dependent activation of KLF4 is required for PDGF-BB-induced phenotypic modulation of smooth muscle.
Article in American journal of physiology. Heart and circulatory physiology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 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
101 citing papers in PubMed, 154 citations in OpenAlex.
- Current Insights into the Molecular Mechanisms of Intracranial Atherosclerosis and Their Therapeutic Implications.International journal of molecular sciences · 2026Review
- Single-Cell Multimodal Profiling Highlights Persistent Aortic Smooth Muscle Cell Changes in Diabetic Mice Despite Glycemic Control.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Sentrin-specific protease 3 (SENP3)-mediated Krüppel-like factor 4 (KLF4) deSUMOylation regulates vascular smooth muscle cell phenotypic switching in atherosclerosis.Molecular biomedicine · 2025Article
- Role of vascular smooth muscle phenotypic transformation induced by histone modifications in the development of abdominal aortic aneurysms.Clinical epigenetics · 2025Review
- Epigenetic alteration of smooth muscle cells regulates endothelin-dependent blood pressure and hypertensive arterial remodeling.The Journal of clinical investigation · 2025Article
- Review
- Epsins oversee smooth muscle cell reprograming by influencing master regulators KLF4 and OCT4.bioRxiv : the preprint server for biology · 2024Article
- Basal ATP release signals through the P2YAtherosclerosis · 2024Article
- N6-methyladenosine-driven miR-143/145-KLF4 circuit orchestrates the phenotypic switch of pulmonary artery smooth muscle cells.Cellular and molecular life sciences : CMLS · 2024Article
- An update on ox-LDL-inducing vascular smooth muscle cell-derived foam cells in atherosclerosis.Frontiers in cell and developmental biology · 2024Review
- 4,4'-Methylene diphenyl diisocyanate exposure induces expression of alternatively activated macrophage-associated markers and chemokines partially through Krüppel-like factor 4 mediated signaling in macrophages.Xenobiotica; the fate of foreign compounds in biological systems · 2023Article
- FAM3A reshapes VSMC fate specification in abdominal aortic aneurysm by regulating KLF4 ubiquitination.Nature communications · 2023Article
- Multi-omics in thoracic aortic aneurysm: the complex road to the simplification.Cell & bioscience · 2023Review
- Roles of Vascular Smooth Muscle Cells in Atherosclerotic Calcification.Journal of lipid and atherosclerosis · 2023Article
- Smooth Muscle Cell Phenotypic Switch Induced by Traditional Cigarette Smoke Condensate: A Holistic Overview.International journal of molecular sciences · 2023Article
- Smooth muscle cells-specific loss of OCT4 accelerates neointima formation after acute vascular injury.Frontiers in cardiovascular medicine · 2023Article
- Somatic Variants in SVIL in Cerebral Aneurysms.Neurology. Genetics · 2022Article
- Phosphorylation of the smooth muscle master splicing regulator RBPMS regulates its splicing activity.Nucleic acids research · 2022Article
- miR-335-5p regulates the proliferation, migration and phenotypic switching of vascular smooth muscle cells in aortic dissection by directly regulating SP1.Acta biochimica et biophysica Sinica · 2022Article
- Nintedanib regulates intestinal smooth muscle hyperplasia and phenotype in vitro and in TNBS colitis in vivo.Scientific reports · 2022Article
41 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
3 authors at 1 institution in 1 country.
Funding
Abstract
There is clear evidence that the phenotypic modulation of smooth muscle cells (SMCs) contributes to the pathophysiology of vascular disease. Phenotypic modulation refers to the unique ability of SMCs to alter their phenotype in response to extracellular stimuli and is hallmarked by the loss of SMC marker gene expression. The transcription factor Krüppel-like factor 4 (KLF4) is a known powerful negative regulator of SMC marker gene expression that works, in part, by decreasing the expression of the serum response factor (SRF) myocardin. KLF4 is not expressed in healthy adult SMCs but is increased in SMCs in response to vascular injury in vivo or PDGF-BB treatment in vitro. The aim of the present study was to determine the molecular mechanisms that regulate the expression of KLF4 in phenotypically modulated SMCs. The results demonstrated that the transcription factor stimulating protein-1 (Sp1) regulated the expression of KLF4 in SMCs. The KLF4 promoter contains three consensus Sp1 binding sites. Using a series of truncated KLF4 promoters, we showed that only fragments containing these Sp1 sites could be activated by PDGF-BB. In addition, overexpression of Sp1 alone was sufficient to increase the activity of the KLF4 promoter. Moreover, inhibiting Sp1 expression with small-interfering RNA attenuated the effects of PDGF-BB on KLF4 expression. Mutation of the three Sp1 sites within the KLF4 promoter abolished both baseline and PDGF-BB-induced activity. Finally, the results demonstrated enhanced Sp1 binding to the KLF4 promoter in SMCs treated with PDGF-BB in vitro and following vascular injury in vivo. Taken together, the results suggest a novel role for Sp1 in increasing the expression of KLF4 in phenotypically modulated SMCs.
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.