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Increase, Inflammation leads to EMT
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding||Point of Contact||Author Status||OECD Status|
|Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis||adjacent||Jinhee Choi (send email)||Under development: Not open for comment. Do not cite||Under Development|
|α-diketone-induced bronchiolitis obliterans||adjacent||Not Specified||Not Specified||Marvin Martens (send email)||Under development: Not open for comment. Do not cite|
Life Stage Applicability
Key Event Relationship Description
The inflammatory reactions initiated by the damaged airway epithelium might stimulate the transition of fibroblasts present in the underlying mesenchymal tissue to myofibroblasts.
Evidence Collection Strategy
Evidence Supporting this KER
Fibroblast to myofibroblast transition might represent an alternative way, besides EMT, to close wounds in the epithelial layer. Under the influence of inflammatory signals, fibroblast present in the mesenchymal tissue beneath the damage epithelium might be stimulated to differentiate into myofibroblasts. Especially in regions of the airways that became completely denuded from an epithelial layer this might form an alternative for EMT to repair the wound in the epithelium.
Studying airway fibroblasts in vitro, myofibroblast transdifferentiation in response to TGF-beta1 signaling was observed, evidenced by increased alpha-smooth muscle actin mRNA and protein expression (Ramirez et al. 2006).
Uncertainties and Inconsistencies
Both the transition of epithelial cells to mesenchymal cells as well as the transition of mesenchymal fibroblasts to myofibroblast are possible mechanisms leading to dysregulated repair of damage airway epithelium. At present it is unclear which transition is the most prominent.
Known modulating factors
Quantitative Understanding of the Linkage
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Ramirez, A. M., Shen, Z., Ritzenthaler, J. D., & Roman, J. (2006). Myofibroblast Transdifferentiation in Obliterative Bronchiolitis: TGF-β Signaling Through Smad3-Dependent and -Independent Pathways. American Journal of Transplantation, 6(9), 2080–2088. https://doi.org/10.1111/j.1600-6143.2006.01430.x