ArticleNature communications2018
A positive feedback loop bi-stably activates fibroblasts.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 2 of them syntheses that pooled it.
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
79 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.
- Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation.Nature communications · 2024Pooled it
- Fibroblasts in Scar Formation: Biology and Clinical Translation.Oxidative medicine and cellular longevity · 2022Pooled it
- Matrix Stiffness Enhances Odontogenic Differentiation of DPSCs through Membrane Curvature Protein Baiap2-Modulated Exosome Release.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Decoding sequence determinants of gene expression in diverse cellular and disease states.Nature methods · 2026Article
- Epigenome regulators imbue a single eukaryotic promoter with diverse gene expression dynamics.iScience · 2026Article
- Cellular and molecular regulation of fibrotic postoperative abdominal adhesions.American journal of physiology. Cell physiology · 2026Review
- In Vivo CRISPR Screening Identifies the Glutamate Receptor GRIA2 as Promoting Peritoneal Metastasis of Gastric Cancer via Calcium-Dependent β-Catenin Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Plant pathogenic nematode exosomes remodel vector tracheae to enhance pathogen transmission.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Epitranscriptomics as a Candidate Universal Modulator of Dormancy Transitions.Ecology and evolution · 2026Review
- Transgelin defines pro-tumorigenic cancer-associated fibroblasts in pancreatic cancer.British journal of cancer · 2026Article
- Cross-talk between cancer-associated fibroblasts and dormant cancer cells: current status and promising therapeutic potential.Cancer cell international · 2025Review
- Uncovering an antifibrotic Prrx1-lineage mesenchymal cell subpopulation in fibrotic lungs.Disease models & mechanisms · 2025Article
- Exploring cellular changes in ruptured human quadriceps tendons at single-cell resolution.The Journal of physiology · 2025Article
- Starvation activates ECM-remodeling gene transcription and putative enhancers in fibroblasts despite inducing quiescence.Cell reports · 2025Article
- Transcription factor networks in cellular quiescence.Nature cell biology · 2025Review
- Review
- Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2.Cell reports. Medicine · 2024Article
- Nutrient starvation activates ECM remodeling gene enhancers associated with inflammatory bowel disease risk in fibroblasts.bioRxiv : the preprint server for biology · 2024Article
- Epithelial-mesenchymal transition in tissue repair and degeneration.Nature reviews. Molecular cell biology · 2024Review
- Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.Nature reviews. Molecular cell biology · 2024Review
19 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
6 authors at 4 institutions in 1 country.
Funding
Abstract
Although fibroblasts are dormant in normal tissue, they exhibit explosive activation during wound healing and perpetual activation in pathologic fibrosis and cancer stroma. The key regulatory network controlling these fibroblast dynamics is still unknown. Here, we report that Twist1, a key regulator of cancer-associated fibroblasts, directly upregulates Prrx1, which, in turn, increases the expression of Tenascin-C (TNC). TNC also increases Twist1 expression, consequently forming a Twist1-Prrx1-TNC positive feedback loop (PFL). Systems biology studies reveal that the Twist1-Prrx1-TNC PFL can function as a bistable ON/OFF switch and regulates fibroblast activation. This PFL can be irreversibly activated under pathologic conditions, leading to perpetual fibroblast activation. Sustained activation of the Twist1-Prrx1-TNC PFL reproduces fibrotic nodules similar to idiopathic pulmonary fibrosis in vivo and is implicated in fibrotic disease and cancer stroma. Considering that this PFL is specific to activated fibroblasts, Twist1-Prrx1-TNC PFL may be a fibroblast-specific therapeutic target to deprogram perpetually activated fibroblasts.
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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.