Pubblicazioni

Autori:

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

Titolo:

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

ISSN Rivista:

1742-4658

N° Volume:

Online ahead of print

Numero o Fascicolo:

Mar 3

Editore:

Blackwell Sinergy

Intervallo pagine:

1-1

Parole chiave:

CRISPR/Cas9; cystic fibrosis; epithelial–mesenchymal transition; organ‐on‐a‐chip; proteomics

Breve descrizione dei contenuti:

: 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

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