ArticleRespiratory research2016
Regulation of transforming growth factor-beta1 (TGF-β1)-induced pro-fibrotic activities by circadian clock gene BMAL1.
Article in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 98 citations in OpenAlex.
- BMAL1 attenuates myocardial infarction-induced fibrosis via suppressing p-SMAD3/SMAD3 in TGF-β1 pathway.Biochemistry and biophysics reports · 2026Article
- A temporal dialogue between the circadian clock and chronic inflammatory diseases.Disease models & mechanisms · 2026Review
- High glucose upregulates BMAL1 in chondrocytes from macroscopically normal and osteoarthritic human cartilage but this only results in increased collagen synthesis in chondrocytes from macroscopically normal cartilage regions.Osteoarthritis and cartilage open · 2026Article
- Circadian rhythm in immunotherapy and cellular therapy: impacts on the tumor microenvironment.Acta biochimica et biophysica Sinica · 2026Review
- Review
- Time to Reset: The Interplay Between Circadian Rhythms and Redox Homeostasis in Skeletal Muscle Ageing and Systemic Health.Antioxidants (Basel, Switzerland) · 2025Review
- BMAL1 Regulates Collagen Production in the Myometrium and Leiomyomas.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- The role of the TGF-β1 signaling pathway in the process of amelogenesis.Frontiers in physiology · 2025Review
- Circadian clocks and their role in kidney and eye diseases across organ systems.Frontiers in physiology · 2025Review
- [Mechanism of melatonin regulating the expression level of rhythm genes to alleviate interstitial pulmonary fibrosis].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- The Potential Diagnostic Utility of SMAD4 and ACCS in the Context of Inflammation in Type 2 Diabetes Mellitus Patients.Biomedicines · 2024Article
- Circadian patterns of growth factor receptor-dependent signaling and implications for carcinogenesis.Cell communication and signaling : CCS · 2024Review
- Article
- Circadian Rhythms in Cardiovascular Metabolism.Circulation research · 2024Review
- Differential Photosensitivity of Fibroblasts Obtained from Normal Skin and Hypertrophic Scar Tissues.International journal of molecular sciences · 2024Article
- Cinobufagin disrupts the stability of lipid rafts by inhibiting the expression of caveolin-1 to promote non-small cell lung cancer cell apoptosis.Archives of medical science : AMS · 2024Article
- Hypoxia Induces Alterations in the Circadian Rhythm in Patients with Chronic Respiratory Diseases.Cells · 2023Review
- Circadian Disruption in Night Shift Work and Its Association with Chronic Pulmonary Diseases.Advanced biology · 2023Review
- Untargeted Metabolomics Reveals Alterations of Rhythmic Pulmonary Metabolism in IPF.Metabolites · 2023Article
- Reciprocal regulation between the molecular clock and kidney injury.Life science alliance · 2023Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundBMAL1 is a transcriptional activator of the molecular clock feedback network. Besides its role in generating circadian rhythms, it has also been shown to be involved in the modulation of cell proliferation, autophagy and cancer cell invasion. However, the role of BMAL1 in pulmonary fibrogenesis is still largely unknown. In this study, we investigated the crosstalk between BMAL1 and the signaling transduction and cellular activities of TGF-β1, a key player in lung fibrogenesis.
methodsLungs from wild type and TGF-β1-adenovirus-infected mice were harvested and homogenized for isolation of RNA and protein. RT-PCR and Western Blotting were employed to measure the expression level of clock genes and TGF-β1-induced downstream target genes. siRNA against human BMAL1 gene was transfected by using lipofectamine RNAiMAX to knockdown the endogenous BMAL1 in both lung epithelial cells and fibroblasts.
resultsOur results showed that TGF-β1 is able to up-regulate BMAL1 expression in both lung epithelial cells and normal lung fibroblasts. In animal models of pulmonary fibrosis, BMAL1 expression was also significantly higher in adenovirus-TGF-β1-infected mice than in the control group. Interestingly, BMAL1 was mostly found in a deacetylated form in the presence of TGF-β1. Importantly, siRNA-mediated knockdown of BMAL1 significantly attenuated the canonical TGF-β1 signaling pathway and altered TGF-β1-induced epithelial-mesenchymal transition and MMP9 production in lung epithelial cells. In addition, BMAL1 knockdown inhibited the fibroblast to myofibroblast differentiation of normal human lung fibroblasts.
conclusionsOur results indicate that activation of TGF-β1 promotes the transcriptional induction of BMAL1. Furthermore, BMAL1 is required for the TGF-β1-induced signaling transduction and pro-fibrotic activities in the lung.
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