ArticleJCI insight2020
Smooth muscle-derived progenitor cell myofibroblast differentiation through KLF4 downregulation promotes arterial remodeling and fibrosis.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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
32 citing papers in PubMed, 52 citations in OpenAlex.
- Novel netrin-1-Unc5b-Klf4 axis balances AT2 survival in experimental bronchopulmonary dysplasia.American journal of respiratory cell and molecular biology · 2026Article
- A rare pre-existing progenitor-like Primed SMC compartment is the dominant inferred source of SMC-derived cellularity in vascular injury and atherosclerosis.bioRxiv : the preprint server for biology · 2026Article
- Contribution of Gli1Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chromatin Remodeling in VSMC Phenotype Switching During Vascular Remodeling: From Mechanism to Therapeutic Potential.Biomolecules · 2026Review
- Fibroblast-Specific Loss of TGF-β Signaling Mediates Lipomatous Metaplasia in the Infarcted Heart.Circulation · 2025Article
- Comprehensive Identification of the Bovine KLF Gene Family and Its Functional Regulation in Muscle Development: Insights from Single-Nuclei Transcriptomics.Animals : an open access journal from MDPI · 2025Article
- Article
- Single-cell RNA sequencing of the carotid artery and femoral artery of rats exposed to hindlimb unloading.Cellular and molecular life sciences : CMLS · 2025Article
- Increased perivascular fibrosis and pro-fibrotic cellular transition in intramyocardial blood vessels in myocardial infarction patients.Journal of molecular and cellular cardiology plus · 2024Article
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- Hormonal influence: unraveling the impact of sex hormones on vascular smooth muscle cells.Biological research · 2024Review
- Integrative gene regulatory network analysis discloses key driver genes of fibromuscular dysplasia.Nature cardiovascular research · 2024Article
- Parathyroid hormone-PTH1R signaling in cardiovascular disease and homeostasis.Trends in endocrinology and metabolism: TEM · 2024Review
- Cardiac and perivascular myofibroblasts, matrifibrocytes, and immune fibrocytes in hypertension; commonalities and differences with other cardiovascular diseases.Cardiovascular research · 2024Review
- [Influences and mechanism of extracellular vesicles from dermal papilla cells of mice on human hypertrophic scar fibroblasts].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2024Article
- Smooth muscle-derived adventitial progenitor cells direct atherosclerotic plaque composition complexity in a Klf4-dependent manner.JCI insight · 2023Article
- Infused juice concentrate of Japanese plum Prunus mume attenuates inflammatory vascular remodeling in a mouse model of hypertension induced by angiotensin II.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- The TNFThe American journal of pathology · 2023Article
- MiR-449a downregulation alleviates the progression of renal interstitial fibrosis by mediating the KLF4/MFN2 axis.International urology and nephrology · 2023Article
- Mammalian organ regeneration in spiny mice.Journal of muscle research and cell motility · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Resident vascular adventitial SCA1+ progenitor (AdvSca1) cells are essential in vascular development and injury. However, the heterogeneity of AdvSca1 cells presents a unique challenge in understanding signaling pathways orchestrating their behavior in homeostasis and injury responses. Using smooth muscle cell (SMC) lineage-tracing models, we identified a subpopulation of AdvSca1 cells (AdvSca1-SM) originating from mature SMCs that undergo reprogramming in situ and exhibit a multipotent phenotype. Here we employed lineage tracing and RNA-sequencing to define the signaling pathways regulating SMC-to-AdvSca1-SM cell reprogramming and AdvSca1-SM progenitor cell phenotype. Unbiased hierarchical clustering revealed that genes related to hedgehog/WNT/beta-catenin signaling were significantly enriched in AdvSca1-SM cells, emphasizing the importance of this signaling axis in the reprogramming event. Leveraging AdvSca1-SM-specific expression of GLI-Kruppel family member GLI1 (Gli1), we generated Gli1-CreERT2-ROSA26-YFP reporter mice to selectively track AdvSca1-SM cells. We demonstrated that physiologically relevant vascular injury or AdvSca1-SM cell-specific Kruppel-like factor 4 (Klf4) depletion facilitated the proliferation and differentiation of AdvSca1-SM cells to a profibrotic myofibroblast phenotype rather than macrophages. Surprisingly, AdvSca1-SM cells selectively contributed to adventitial remodeling and fibrosis but little to neointima formation. Together, these findings strongly support therapeutics aimed at preserving the AdvSca1-SM cell phenotype as a viable antifibrotic approach.
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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.