The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression
Open accessAbstract
Tissue stiffening is a hallmark of fibrotic disorders but has traditionally been regarded as an outcome of fibrosis, not a contributing factor to pathogenesis. In this study, we show that fibrosis induced by bleomycin injury in the murine lung locally increases median tissue stiffness sixfold relative to normal lung parenchyma. Across this pathophysiological stiffness range, cultured lung fibroblasts transition from a surprisingly quiescent state to progressive increases in proliferation and matrix synthesis, accompanied by coordinated decreases in matrix proteolytic gene expression. Increasing matrix stiffness strongly suppresses fibroblast expression of COX-2 (cyclooxygenase-2) and synthesis of prostaglandin E2 (PGE2), an autocrine inhibitor of fibrogenesis. Exogenous PGE2 or an agonist of the prostanoid EP2 receptor completely counteracts the proliferative and matrix synthetic effects caused by increased stiffness. Together, these results demonstrate a dominant role for normal tissue compliance, acting in part through autocrine PGE2, in maintaining fibroblast quiescence and reveal a feedback relationship between matrix stiffening, COX-2 suppression, and fibroblast activation that promotes and amplifies progressive fibrosis.
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Cites
Matrix elasticity directs stem cell lineage specification
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006) · Cell · doi:10.1016/j.cell.2006.06.044 · Cited by 13,915
Cellular and molecular mechanisms of fibrosis
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Myofibroblasts and mechano-regulation of connective tissue remodelling
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Cell Movement Is Guided by the Rigidity of the Substrate
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Effects of substrate stiffness on cell morphology, cytoskeletal structure, and adhesion
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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
Acute Exacerbations of Idiopathic Pulmonary Fibrosis
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Self-citationThe Clinical Course of Patients with Idiopathic Pulmonary Fibrosis
Martinez, F. J., Safrin, S., Weycker, D., Starko, K. M., Bradford, W. Z., King, T. E., Flaherty, K. R., Schwartz, D. A., Noble, P. W., Raghu, G., et al. (2005) · Annals of Internal Medicine · doi:10.7326/0003-4819-142-12_part_1-200506210-00005 · Cited by 622
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
Cited by
Mechanotransduction and extracellular matrix homeostasis
Humphrey, J. D., Dufresne, E. R., & Schwartz, M. A. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3896 · Cited by 2,124
Richeldi, L., Collard, H. R., & Jones, M. G. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30866-8 · Cited by 2,020
Martinez, F. J., Collard, H. R., Pardo, A., Raghu, G., Richeldi, L., Selman, M., Swigris, J. J., Taniguchi, H., & Wells, A. U. (2017) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2017.74 · Cited by 1,388
Recent Developments in Myofibroblast Biology
Hinz, B., Phan, S. H., Thannickal, V. J., Prunotto, M., Desmoulière, A., Varga, J., De Wever, O., Mareel, M., & Gabbiani, G. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2012.02.004 · Cited by 1,193
Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound
Tracy, L. E., Minasian, R. A., & Caterson, E. J. (2016) · Advances in Wound Care · doi:10.1089/wound.2014.0561 · Cited by 1,008
Metadata
- Authors
- Liu, F., Mih, J. D., Shea, B. S., Kho, A. T., Sharif, A. S., Tager, A. M., & Tschumperlin, D. J.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2010-08-23
- Volume
- 190
- Issue
- 4
- Pages
- 693-706
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2159731793
- Cited by
- 810
- References
- 12
- FWCI
- 25.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Liu, F., Mih, J. D., Shea, B. S., Kho, A. T., Sharif, A. S., Tager, A. M., & Tschumperlin, D. J. (2010). Feedback amplification of fibrosis through matrix stiffening and COX-2 suppression. Journal of Cell Biology. https://doi.org/10.1083/jcb.201004082
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
