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Increased extracellular matrix deposition leads to Pulmonary fibrosis
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Fibrosis by definition is the end result of a healing process. It involves a series of lung remodelling and reorganisation events leading to permanent alteration in the lung architecture and a fixed scar tissue or fibrotic lesion (Wallace WA, 2007). Excessive deposition of ECM or collagen is the hallmark of this disease and there is ample evidence to support this KER (Fukuda 1985, Meyer 2017, Richeldi 2017, Thannickal 2004, Zisman 2005).
Evidence Collection Strategy
Evidence Supporting this KER
By definition, pulmonary fibrosis is characterized by excessive deposition of extracellular matrix and destruction of native lung architecture (Fukuda 1985, Richeldi 2017, Thannickal 2004). Thus, the plausibility of this association is undisputed.
Uncertainties and Inconsistencies
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Humans (Zisman 2005, Meyer 2017), rats (Williamson 2015), mice (Williamson 2015).
- Fukuda Y, Ferrans VJ, Schoenberger CI, Rennard SI, Crystal RG. Patterns of pulmonary structural remodeling after experimental paraquat toxicity. The morphogenesis of intraalveolar fibrosis. Am J Pathol. 1985;118(3):452–475.
- Meyer K. C. (2017). Pulmonary fibrosis, part I: epidemiology, pathogenesis, and diagnosis. Expert review of respiratory medicine, 11(5), 343–359. https://doi.org/10.1080/17476348.2017.1312346
- Richeldi, L., Collard, H. R., & Jones, M. G. (2017). Idiopathic pulmonary fibrosis. Lancet (London, England), 389(10082), 1941–1952. https://doi.org/10.1016/S0140-6736(17)30866-8
- Thannickal, V. J., Toews, G. B., White, E. S., Lynch, J. P., 3rd, & Martinez, F. J. (2004). Mechanisms of pulmonary fibrosis. Annual review of medicine, 55, 395–417. https://doi.org/10.1146/annurev.med.55.091902.103810
- Wallace, W., Fitch, P., Simpson, A. and Howie, S. (2006). Inflammation-associated remodelling and fibrosis in the lung - a process and an end point. International Journal of Experimental Pathology, 88(2), pp.103-110
- Williamson, J. D., Sadofsky, L. R., & Hart, S. P. (2015). The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis. Experimental lung research, 41(2), 57–73. https://doi.org/10.3109/01902148.2014.979516
- Zisman, D. A., Keane, M. P., Belperio, J. A., Strieter, R. M., & Lynch, J. P., 3rd (2005). Pulmonary fibrosis. Methods in molecular medicine, 117, 3–44. https://doi.org/10.1385/1-59259-940-0:003