ArticleProceedings of the National Academy of Sciences of the United States of America2020
The circadian clock protein REVERBα inhibits pulmonary fibrosis development.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 89 citations in OpenAlex.
- Circadian mechanisms in heart failure: Cell-specific regulation and chrono-medicine.Cell insight · 2026Review
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- The circadian clock controls hepatic stellate cell activation via a BMAL1/CK1ε/REV-ERBα/transgelin signaling pathway.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Uremic toxins promote renal fatty acid synthesis and fibrosis via activating aryl hydrocarbon receptor.Nature communications · 2026Article
- Adrenaline restores Bmal1 transcriptional rhythms dampened by SARS-CoV-2 infection in Cthrc1-positive pulmonary fibroblasts derived from the Nile grass rat.Scientific reports · 2026Article
- A temporal dialogue between the circadian clock and chronic inflammatory diseases.Disease models & mechanisms · 2026Review
- The Interplay Between Circadian Clocks and the Tumour Microenvironment in Breast Cancer.Cancers · 2026Review
- STL1267 inhibits myofibroblast differentiation in a TGFβ1-driven human lung fibroblast model.American journal of physiology. Cell physiology · 2026Article
- The circadian clock component PER2 deficiency aggravates airway epithelial remodeling through Wnt/β-catenin signaling pathway.Respiratory research · 2026Article
- The cGAS-STING pathway in fibroblast microenvironment: from molecular mechanisms to targeted therapies.Apoptosis : an international journal on programmed cell death · 2026Review
- Circadian disruption and circulating TGF-β1 in workers: evidence from Mendelian randomization and observational data.Frontiers in immunology · 2026Observational
- Circadian clock regulation in lung health and disease: molecular mechanisms and therapeutic opportunities.EXCLI journal · 2026Review
- Downregulation of RORα by alcohol promotes TGFβ and α-SMA expression in mouse lung fibroblasts.Frontiers in medicine · 2026Article
- Natural bioactive compounds targeting the macrophage clock in asthma: evidence, challenges, and perspectives.Frontiers in immunology · 2026Review
- Circadian clock genes: Their influence on liver metabolism, disease development and treatment (Review).Molecular medicine reports · 2026Review
- Review
- Perturbation of the circadian clock in chronic diseases involving organ fibrosis.The Journal of clinical investigation · 2025Review
- Time to Reset: The Interplay Between Circadian Rhythms and Redox Homeostasis in Skeletal Muscle Ageing and Systemic Health.Antioxidants (Basel, Switzerland) · 2025Review
- Clock pathway inhibitor overcomes tumor immune-exclusion via regulation of fibrocyte differentiation.NPJ precision oncology · 2025Article
- Pharmacological manipulation of liver fibrosis progression using novel HDAC6 inhibitors.The FEBS journal · 2025Article
8 more citing papers are in PubMed but not listed here.
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24 authors at 7 institutions in 3 countries.
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Abstract
Pulmonary inflammatory responses lie under circadian control; however, the importance of circadian mechanisms in the underlying fibrotic phenotype is not understood. Here, we identify a striking change to these mechanisms resulting in a gain of amplitude and lack of synchrony within pulmonary fibrotic tissue. These changes result from an infiltration of mesenchymal cells, an important cell type in the pathogenesis of pulmonary fibrosis. Mutation of the core clock protein REVERBα in these cells exacerbated the development of bleomycin-induced fibrosis, whereas mutation of REVERBα in club or myeloid cells had no effect on the bleomycin phenotype. Knockdown of REVERBα revealed regulation of the little-understood transcription factor TBPL1. Both REVERBα and TBPL1 altered integrinβ1 focal-adhesion formation, resulting in increased myofibroblast activation. The translational importance of our findings was established through analysis of 2 human cohorts. In the UK Biobank, circadian strain markers (sleep length, chronotype, and shift work) are associated with pulmonary fibrosis, making them risk factors. In a separate cohort, REVERBα expression was increased in human idiopathic pulmonary fibrosis (IPF) lung tissue. Pharmacological targeting of REVERBα inhibited myofibroblast activation in IPF fibroblasts and collagen secretion in organotypic cultures from IPF patients, thus suggesting that targeting of REVERBα could be a viable therapeutic 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.