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Accumulation, Collagen leads to Pulmonary fibrosis
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Latent Transforming Growth Factor beta1 activation leads to pulmonary fibrosis||adjacent||High||Cataia Ives (send email)||Under development: Not open for comment. Do not cite|
|Substance interaction with the pulmonary resident cell membrane components leading to pulmonary fibrosis||adjacent||High||Low||Cataia Ives (send email)||Under development: Not open for comment. Do not cite||EAGMST Under Review|
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 extracellular matrix (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 ECM 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 Mar;118(3):452-75.
- Meyer KC. Pulmonary fibrosis, part I: epidemiology, pathogenesis, and diagnosis. Expert Rev Respir Med. 2017 May;11(5):343-359. doi: 10.1080/17476348.2017.1312346.
- Richeldi L, Collard HR, Jones MG. Idiopathic pulmonary fibrosis. Lancet. 2017 May 13;389(10082):1941-1952. doi: 10.1016/S0140-6736(17)30866-8.
- Thannickal VJ, Toews GB, White ES, Lynch JP 3rd, Martinez FJ. Mechanisms of pulmonary fibrosis. Annu Rev Med. 2004;55:395-417. doi: 10.1146/annurev.med.55.091902.103810.
- Wallace WA, Fitch PM, Simpson AJ, Howie SE. Inflammation-associated remodelling and fibrosis in the lung - a process and an end point. Int J Exp Pathol. 2007 Apr;88(2):103-10. doi: 10.1111/j.1365-2613.2006.00515.x.
- Williamson JD, Sadofsky LR, Hart SP. The pathogenesis of bleomycin-induced lung injury in animals and its applicability to human idiopathic pulmonary fibrosis. Exp Lung Res. 2015 Mar;41(2):57-73. doi: 10.3109/01902148.2014.979516.
- Zisman DA, Keane MP, Belperio JA, Strieter RM, Lynch JP 3rd. Pulmonary fibrosis. Methods Mol Med. 2005;117:3-44. doi: 10.1385/1-59259-940-0:003.