Relationship: 1724
Title
Upstream event
Increase, InflammationDownstream event
EMT
Key Event Relationship Overview
AOPs Referencing Relationship
| AOP Name | Adjacency | Weight of Evidence | Quantitative Understanding |
|---|---|---|---|
| Peroxisome proliferator-activated receptors γ inactivation leading to lung fibrosis | adjacent | ||
| α-diketone-induced bronchiolitis obliterans | adjacent | Not Specified | Not Specified |
Taxonomic Applicability
Sex Applicability
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 Supporting this KER
Biological Plausibility
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.
Empirical Evidence
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.
Quantitative Understanding of the Linkage
Domain of Applicability
References
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