A study on the Epithelial-mesenchymal transition in animal model of cicatricial airway stenosis
W. Tinga (Dr), L. Yanpinga (Dr), L. Yana (Dr), N. Jinmua (Dr), Z. Jie*a (Prof)
a Beijing Tiantan Hospital, Capital Medical University, Beijing, CHINA
Background The treatment of cicatricial airway stenosis is currently a difficult problem in the field of interventional pulmonology. The pathogenesis is still unclear and studies are limited. Several studies have confirmed the transformation of tracheal epithelial cells into mesenchymal cells (Epithelial-mesenchymal transition, EMT) during the airway remodeling which occurred after lung transplantation, however, whether this machenism works in the process of cicatricial airway stenosis is unclear. In this study, we intend to study the damage and repair of airway epithelial cells in cicatricial airway stenosis and the imbalance of epithelial/mesenchymal cells, in order to explore the mechanism of the formation of cicatricial airway stenosis.
Methods Eight rabbit cicatricial airway stenosis animal models were established. Normal airway epithelium and airway scar tissue specimens from animal models at different time points (14 days, 1 month, 2 months, and 3 months after epithelial injury) were obtained. The progressive expression of the epithelial marker (E-Cadherin) and the mesenchymal marker (α-smooth muscle actin, α-SMA), and the ratio between them were compared. The progressive expression of EMT marker (MMP-9) were also observed to confirm whether EMT occurred in cicatricial airway stenosis and the relationship between the degree of EMT and the cicatricial airway stenosis formation.
Results Compared with the normal airway epithelium, the expression of E-Cadherin was down-regulated in airway scar tissue, the expression of α- SMA was up-regulated, and the ratio of E-Cadherin to α-SMA was decreased, too. With the progress of cicatricial airway stenosis, the expression of MMP-9 was increased progressively.
Conclusions The cicatricial airway stenosis formed after the injury of the airway mucosa in rabbits has the process of EMT. With the progress of cicatricial airway stenosis, the degree of epithelial cells to mesenchymal transition was increased. This may provide new therapeutic targets for the disease.
Disclosure of funding source(s):
This study was supported by the grant from Beijing Municipal Administration of Hospitals Incubating Program (grantnumber:PX2021022) and Beijing Municipal Key Clinical Specialty Project(grantno.2020-129).