Inflammation and epithelial-mesenchymal transition in a CFTR-depleted human bronchial epithelial cell line revealed by proteomics and human organ-on-a-chip
Inflammation and epithelial-mesenchymal transition in a CFTR-depleted human bronchial epithelial cell line revealed by proteomics and human organ-on-a-chip
(2025)
Inflammation and epithelial-mesenchymal transition in a CFTR-depleted human bronchial epithelial cell line revealed by proteomics and human organ-on-a-chip
Anno:
2025
Tipologia prodotto:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Lingua:
Inglese
Referee:
No
Nome rivista:
FEDERATION OF EUROPEAN BIOCHEMICAL SOCIETIES JOURNAL
: Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, leading to chronic, unresolved inflammation of the airways due to uncontrolled recruitment of polymorphonuclear leukocytes (PMNs). Evidence indicates that CFTR loss-of-function, in addition to promoting a pro-inflammatory phenotype, is associated with an increased risk of developing cancer, suggesting that CFTR can exert tumor-suppressor functions. Three-dimensional (3D) in vitro culture models, such as the CF lung airway-on-a-chip, can be suitable for studying PMN recruitment, as well as events of cancerogenesis, that is epithelial cell invasion and migration, in CF. To gather insight into the pathobiology of CFTR loss-of-function, we generated CFTR-knockout (KO) clones of the 16HBE14o- human bronchial cell line by CRISPR/Cas9 gene editing, and performed a comparative proteomic analysis of these clones with their wild-type (WT) counterparts. Systematic signaling pathway analysis of CFTR-KO clones revealed modulation of inflammation, PMN recruitment, epithelial cell migration, and epithelial-mesenchymal transition. Using a latest-generation organ-on-a-chip microfluidic platform, we confirmed that CFTR-KO enhanced PMN recruitment and epithelial cell invasion of the endothelial layer. Thus, a dysfunctional CFTR affects multiple pathways in the airway epithelium that ultimately contribute to sustained inflammation and cancerogenesis in CF.
Id prodotto:
144638
Handle IRIS:
11562/1157210
ultima modifica:
8 maggio 2025
Citazione bibliografica:
Mattoscio, Domenico; Baeza, Luis A; Bai, Haiqing; Colangelo, Tommaso; Castagnozzi, Simone; Marzotto, Marta; Cufaro, Maria Concetta; Lotti, Virginia; Yuan, Yu-Chieh; Mucci, Matteo; Si, Longlong; Zuccarini, Mariachiara; Tredicine, Maria; D'Orazio, Simona; Pieragostino, Damiana; Del Boccio, Piero; Sorio, Claudio; Trerotola, Marco; Romano, Mario; Plebani, Roberto,
Inflammation and epithelial-mesenchymal transition in a CFTR-depleted human bronchial epithelial cell line revealed by proteomics and human organ-on-a-chip«FEDERATION OF EUROPEAN BIOCHEMICAL SOCIETIES JOURNAL»
, vol. Online ahead of print
, n. Mar 3
, 2025
, pp. 1-1