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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Citations
Cites
Making sense of latent TGFβ activation
Annes, J. P., Munger, J. S., & Rifkin, D. B. (2002) · Journal of Cell Science · doi:10.1242/jcs.00229 · Cited by 1,624
Myofibroblast contraction activates latent TGF-β1 from the extracellular matrix
Wipff, P.-J., Rifkin, D. B., Meister, J.-J., & Hinz, B. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200704042 · Cited by 1,346
Sime, P. J., Xing, Z., Graham, F. L., Csaky, K. G., & Gauldie, J. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119590 · Cited by 1,050
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
Zhou, Y., Huang, X., Hecker, L., Kurundkar, D., Kurundkar, A., Liu, H., Jin, T. H., Desai, L. P., Bernard, K. F., & Thannickal, V. J. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66700 · Cited by 466
Latent Transforming Growth Factor-β (TGF-β) Binding Proteins: Orchestrators of TGF-β Availability
Rifkin, D. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r400029200 · Cited by 422
Smad3 deficiency attenuates bleomycin-induced pulmonary fibrosis in mice
Zhao, J., Shi, W., Wang, Y., Chen, H., Bringas, P., Datto, M., Frederick, J. P., Wang, X., & Warburton, D. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00151.2001 · Cited by 411
Smad3 Null Mice Develop Airspace Enlargement and Are Resistant to TGF-β-Mediated Pulmonary Fibrosis
Bonniaud, P., Kolb, M. R. J., Galt, T., Robertson, J. V., Robbins, C. S., Stämpfli, M. R., Lavery, C., Margetts, P. J., Roberts, A. B., & Gauldie, J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.173.3.2099 · Cited by 383
Self-citationThe role of proteases in transforming growth factor-β activation
Jenkins, G. R. (2008) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.11.026 · Cited by 374
Self-citationConversion of Mechanical Force into TGF-β-Mediated Biochemical Signals
Maeda, T., Sakabe, T., Sunaga, A., Sakai, K., Rivera, A. L., Keene, D. R., Sasaki, T., Stavnezer, E., Iannotti, J. P., Schweitzer, R., et al. (2011) · Current Biology · doi:10.1016/j.cub.2011.04.007 · Cited by 363
Khalil, N. (1999) · Microbes and Infection · doi:10.1016/s1286-4579(99)00259-2 · Cited by 341
Absence of integrin-mediated TGFβ1 activation in vivo recapitulates the phenotype of TGFβ1-null mice
Yang, Z., Mu, Z., Dabovic, B., Jurukovski, V., Yu, D., Sung, J. J., Xiong, X., & Munger, J. S. (2007) · The Journal of Cell Biology · doi:10.1083/jcb.200611044 · Cited by 330
Khalil, N., O'Connor, R. N., Flanders, K. C., & Unruh, H. W. (1996) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.14.2.8630262 · Cited by 328
Jenkins, G. R. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27183 · Cited by 322
Self-citationJenkins, R. G., Simpson, J. K., Saini, G., Bentley, J. H., Russell, A.-M., Braybrooke, R., Molyneaux, P. L., McKeever, T. M., Wells, A. U., Flynn, A., et al. (2015) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00048-x · Cited by 314
Self-citationThe α v β 1 integrin plays a critical in vivo role in tissue fibrosis
Reed, N. I., Jo, H., Chen, C., Tsujino, K., Arnold, T. D., DeGrado, W. F., & Sheppard, D. (2015) · Science Translational Medicine · doi:10.1126/scitranslmed.aaa5094 · Cited by 311
Pulmonary Fibrosis Correlates With Outcome in Adult Respiratory Distress Syndrome
Martin, C., Papazian, L., Payan, M.-J., SAUX, P., & Gouin, F. (1995) · CHEST Journal · doi:10.1378/chest.107.1.196 · Cited by 272
Matrix control of transforming growth factor- function
Horiguchi, M., Ota, M., & Rifkin, D. B. (2012) · The Journal of Biochemistry · doi:10.1093/jb/mvs089 · Cited by 270
The Single-Molecule Mechanics of the Latent TGF-β1 Complex
Buscemi, L., Ramonet, D., Klingberg, F., Formey, A., Smith-Clerc, J., Meister, J.-J., & Hinz, B. (2011) · Current Biology · doi:10.1016/j.cub.2011.11.037 · Cited by 266
Bonniaud, P., Margetts, P. J., Kolb, M. R. J., SCHROEDER, J., Kapoun, A. M., Damm, D., Murphy, A., Chakravarty, S., Dugar, S., Higgins, L. S., et al. (2004) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200405-612oc · Cited by 266
Self-citationTGF-β and Smad3 Signaling Link Inflammation to Chronic Fibrogenesis
Bonniaud, P., Margetts, P. J., Ask, K., Flanders, K., Gauldie, J., & Kolb, M. R. J. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.8.5390 · Cited by 252
Self-citationAluwihare, P., Mu, Z., Zhao, Z., Yu, D., Weinreb, P. H., Horan, G. S. B., Violette, S. M., & Munger, J. S. (2008) · Journal of Cell Science · doi:10.1242/jcs.035246 · Cited by 229
Extracellular matrix deposition by primary human lung fibroblasts in response to TGF-β1 and TGF-β3
Eickelberg, O., Köhler, E. S., Reichenberger, F., Bertschin, S., Woodtli, T., Erné, P., Perruchoud, A. P., & Roth, M. (1999) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1999.276.5.l814 · Cited by 225
Xu, M. Y., Porte, J., Knox, A. J., Weinreb, P. H., Maher, T. M., Violette, S. M., McAnulty, R. J., Sheppard, D., & Jenkins, G. R. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080160 · Cited by 215
Self-citationIntegrins αvβ5 and αvβ3 promote latent TGF-β1 activation by human cardiac fibroblast contraction
Sarrazy, V., Koehler, A., Chow, M. L., Zimina, E., Li, C. X., Kato, H., Caldarone, C. A., & Hinz, B. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu053 · Cited by 215
Transglutaminase 2 and Its Role in Pulmonary Fibrosis
Olsen, K. C., Sapinoro, R., Kottmann, R. M., Kulkarni, A. A., Iismaa, S. E., Johnson, G. V. W., Thatcher, T. H., Phipps, R. P., & Sime, P. J. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201101-0013oc · Cited by 193
Mechanical stress induces lung fibrosis by epithelial–mesenchymal transition*
Cabrera-Benítez, N. E., Parotto, M., Post, M., Han, B., Spieth, P. M., Cheng, W.-E., Valladares, F., Villar, J., Liu, M., Sato, M., et al. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e31822f09d7 · Cited by 166
Pulmonary Function Testing in Idiopathic Interstitial Pneumonias
Martínez, F. J., & Flaherty, K. (2006) · Proceedings of the American Thoracic Society · doi:10.1513/pats.200602-022tk · Cited by 166
In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-β1
Ahamed, J., Burg, N. D., Yoshinaga, K., Janczak, C. A., Rifkin, D. B., & Coller, B. S. (2008) · Blood · doi:10.1182/blood-2008-04-151753 · Cited by 162
Matrices of Physiologic Stiffness Potently Inactivate Idiopathic Pulmonary Fibrosis Fibroblasts
Marinković, A., Liu, F., & Tschumperlin, D. J. (2012) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2012-0335oc · Cited by 162
Integrin αvβ5-Mediated TGF-β Activation by Airway Smooth Muscle Cells in Asthma
Tatler, A. L., John, A. E., Jolly, L., Habgood, A., Porte, J., Brightling, C. E., Knox, A. J., Pang, L., Sheppard, D., Huang, X., et al. (2011) · The Journal of Immunology · doi:10.4049/jimmunol.1003507 · Cited by 153
Self-citationMarinković, А., Mih, J. D., Park, J., Liu, F., & Tschumperlin, D. J. (2012) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00108.2012 · Cited by 148
Zhou, Y., Hagood, J. S., Lu, B., Merryman, W. D., & Murphy-Ullrich, J. E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.126227 · Cited by 119
Giacomini, M. M., Travis, M. A., Kudo, M., & Sheppard, D. (2012) · Experimental Cell Research · doi:10.1016/j.yexcr.2012.01.020 · Cited by 109
Fasudil, a Rho-Kinase Inhibitor, Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice
Jiang, C., Huang, H. F., Liu, J., Wang, Y., Lu, Z., & Xu, Z. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13078293 · Cited by 96
Regulation of TGF-β storage and activation in the human idiopathic pulmonary fibrosis lung
Leppäranta, O., Sens, C., Salmenkivi, K., Kinnula, V. L., Keski‐Oja, J., Myllärniemi, M., & Koli, K. M. (2012) · Cell and Tissue Research · doi:10.1007/s00441-012-1385-9 · Cited by 77
Sakamoto, S., Homma, S. A., Mun, M., Fujii, T., Kurosaki, A., & Yoshimura, K. (2011) · Internal Medicine · doi:10.2169/internalmedicine.50.3390 · Cited by 74
Villar, J., Cabrera-Benítez, N. E., Valladares, F., Casula, M., Flores, C., Blanch, L. L., Quílez, M. E., Santana-Rodríguez, N., Kacmarek, R. M., & Slutsky, A. S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0023914 · Cited by 73
Comparison between conventional and "clinical" assessment of experimental lung fibrosis
Ask, K., Labiris, R., Farkas, L., Moeller, A., Froese, A., Farncombe, T. H., McClelland, G. B., Inman, M. D., Gauldie, J., & Kolb, M. R. J. (2008) · Journal of Translational Medicine · doi:10.1186/1479-5876-6-16 · Cited by 73
Self-citationHanley, M. E., King, T. E., Schwarz, M. I., Watters, L. C., Shen, A. S., & Cherniack, R. M. (1991) · American Review of Respiratory Disease · doi:10.1164/ajrccm/144.5.1102 · Cited by 64
Jolly, L., Stavrou, A., Vanderstocken, G., Meliopoulos, V., Habgood, A., Tatler, A. L., Porte, J., Knox, A. J., Weinreb, P. H., Violette, S. M., et al. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.582262 · Cited by 56
Self-citationExtracellular matrix microenvironment contributes actively to pulmonary fibrosis
Shimbori, C., Gauldie, J., & Kolb, M. R. J. (2013) · Current Opinion in Pulmonary Medicine · doi:10.1097/mcp.0b013e328363f4de · Cited by 54
Self-citationInhibition of the αvβ6 integrin leads to limited alteration of TGF-α-induced pulmonary fibrosis
Madala, S. K., Korfhagen, T. R., Schmidt, S., Davidson, C. R., Edukulla, R., Ikegami, M., Violette, S. M., Weinreb, P. H., Sheppard, D., & Hardie, W. D. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00357.2013 · Cited by 52
Postoperative Acute Exacerbation of IPF after Lung Resection for Primary Lung Cancer
Watanabe, A., Kawaharada, N., & Higami, T. (2011) · Pulmonary Medicine · doi:10.1155/2011/960316 · Cited by 52
Boo, S., & Dagnino, L. (2013) · Advances in Wound Care · doi:10.1089/wound.2012.0394 · Cited by 29
Cited by
Sorted by citations
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
