The DOI matches its Crossref record; 51 of the 51 references it cites were found in a registry or an index.
Stretch-induced Activation of Transforming Growth Factor-β1 in Pulmonary Fibrosis
Abstract
Rationale: Recent findings suggesting transforming growth factor (TGF)-β1 activation by mechanical stimuli in vitro raised the question of whether this phenomenon was relevant in vivo in the context of pulmonary fibrosis. Objectives: To explore the effect of mechanical stress on TGF-β1 activation and its signaling pathway in rat and human fibrotic lung tissue using a novel ex vivo model. Methods: Rat lung fibrosis was induced using transient gene expression of active TGF-β1. Lungs were harvested at Day 14 or 21 and submitted to various stimuli in a tissue bath equipped with a force transducer and servo-controlled arm. Measurements and Main Results: Fibrotic lung strips responded to tensile force by releasing active TGF-β1 from latent stores with subsequent increase in tissue phospho-Smad2/3. In contrast, measurable active TGF-β1 and phospho-Smad2/3 were not induced by mechanical stress in nonfibrotic lungs. Protease inhibition did not affect the release of active TGF-β1. A TGF-β1 receptor inhibitor, Rho-associated protein kinase inhibitor, and αv integrin inhibitor all attenuated mechanical stretch–induced phospho-Smad2/3 in fibrotic lung strips. Furthermore, the induction of phospho-Smad2/3 was enhanced in whole fibrotic rat lungs undergoing ventilation pressure challenge compared with control lungs. Last, tissue slices from human lung with usual interstitial pneumonia submitted to mechanical force showed an increase in TGF-β1 activation and induction of phospho-Smad2/3 in contrast with human nonfibrotic lungs. Conclusions: Mechanical tissue stretch contributes to the development of pulmonary fibrosis via mechanotransduced activation of TGF-β1 in rodent and human pulmonary fibrosis.
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“However drugs targeting metabolism pathways are approved or in clinical trials for treatment of cancer with known safety profiles, fueling the hope for future application in fibrotic diseases57.”
From Fibrosis: from mechanisms to medicines (2020) · cites this paper as [57]
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Cites
Making sense of latent TGFβ activation
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Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix
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Self-citationLatent TGF-β structure and activation
Shi, M., Zhu, J., Wang, R., Chen, X., Mi, L., Walz, T., & Springer, T. A. (2011) · Nature · doi:10.1038/nature10152 · Cited by 1,013
Barry-Hamilton, V., Spangler, R., Marshall, D., McCauley, S., Rodriguez, H. M., Oyasu, M., Mikels, A., Vaysberg, M., Ghermazien, H., Wai, C., et al. (2010) · Nature Medicine · doi:10.1038/nm.2208 · Cited by 870
Henderson, N. C., Arnold, T. D., Katamura, Y., Giacomini, M. M., Rodriguez, J. D., McCarty, J. H., Pellicoro, A., Raschperger, E., Betsholtz, C., Ruminski, P. G., et al. (2013) · Nature Medicine · doi:10.1038/nm.3282 · Cited by 866
Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression
Liu, F., Mih, J. D., Shea, B. S., Kho, A. T., Sharif, A. S., Tager, A. M., & Tschumperlin, D. J. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201004082 · Cited by 828
Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis
Georges, P. C., Hui, J.-J., Gombos, Z., McCormick, M. E., Wang, A. Y., Uemura, M., Mick, R., Janmey, P. A., Furth, E. E., & Wells, R. G. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00032.2007 · Cited by 577
Matrix stiffness-induced myofibroblast differentiation is mediated by intrinsic mechanotransduction
Huang, X., Yang, N., Fiore, V. F., Barker, T. H., Sun, Y., Morris, S. W., Ding, Q., Thannickal, V. J., & Zhou, Y. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0050oc · Cited by 530
TGF-β – an excellent servant but a bad master
Kubiczkova, L., Sedlarikova, L., Hajek, R., & Sevcikova, S. (2012) · Journal of Translational Medicine · doi:10.1186/1479-5876-10-183 · Cited by 511
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Fibrosis: from mechanisms to medicines
Henderson, N. C., Rieder, F., & Wynn, T. A. (2020) · Nature · doi:10.1038/s41586-020-2938-9 · Cited by 1,868
Transforming growth factor–β in tissue fibrosis
Frangogiannis, N. G. (2019) · The Journal of Experimental Medicine · doi:10.1084/jem.20190103 · Cited by 1,377
Pathogenic Mechanisms Underlying Idiopathic Pulmonary Fibrosis
Moss, B. J., Ryter, S. W., & Rosas, I. O. (2021) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-042320-030240 · Cited by 852
Behr, J., Prasse, A., Kreuter, M., Johow, J., Rabe, K. F., Bonella, F., Bonnet, R., Grohe, C., Held, M., Wilkens, H., et al. (2021) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(20)30554-3 · Cited by 522
The extracellular matrix as a multitasking player in disease
Theocharis, A. D., Manou, D., & Karamanos, N. K. (2019) · FEBS Journal · doi:10.1111/febs.14818 · Cited by 533
Metadata
- Authors
- Froese, A. R., Shimbori, C., Bellaye, P.-S., Inman, M., Obex, S., Fatima, S., Jenkins, G., Gauldie, J., Ask, K., & Kolb, M.
- Affiliations
- St. Joseph’s Healthcare Hamilton (CA)
- University of Nottingham (GB)
- McMaster University (CA)
- Corresponding author
- Kolb, Martin
- Venue
- American Journal of Respiratory and Critical Care Medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-07-01
- Volume
- 194
- Issue
- 1
- Pages
- 84-96
- ISSN
- 1073-449X (ISSN-L)
- 1535-4970
- OpenAlex
- W2260133387
- Cited by
- 214
- References
- 51
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 14 · 2023: 15 · 2022: 25 · 2021: 33 · 2020: 22 · 2019: 27 · 2018: 22 · 2017: 18 · 2016: 6
- FWCI
- 21.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Respiratory and Critical Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pulmonary Fibrosis Foundation I. M. Rosenzweig Junior Investigator Award
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Pulmonary Hypertension Research and Treatments
- Keywords
- pulmonary fibrosis, TGF-β1, mechanical stretch, mechanotransduction, Smad2/3 phosphorylation, latent TGF-beta1 activation, usual interstitial pneumonia, Rho kinase, ITGAV, ventilation pressure
- MeSH terms
- Animals, Disease Models, Animal, Humans, Lung, Pulmonary Fibrosis, Stress, Mechanical, Signal Transduction, Rats, Transforming Growth Factor beta1
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