Airway epithelial dysfunction and mesenchymal transition in chronic obstructive pulmonary disease: Role of Oct-4

Alberto Giuseppe Fucarino, Fabio Bucchieri, Giusy Daniela Albano, Giulia Anzalone, Delphine Gras, Giusy Daniela Albano, Angela Marina Montalbano, Chiara Lo Nigro, Giulia Anzalone, Fabio Bucchieri, Rosalia Gagliardo, Mirella Profita, Pascal Chanez, Roberto Marchese, Chiara Lo Nigro, Roberto Marchese, Rosalia Paola Gagliardo

Risultato della ricerca: Articlepeer review


The airway epithelium is a dynamic tissue that undergoes slow but constant renewal. Dysregulation of airwayepithelial function related to cigarette smoke exposure plays an important role in the pathophysiology of COPD.Oct4 is a transcription factor responsible for maintaining cellular self-renewal and regeneration, and CD146 andCD105/Endoglin are adhesion molecules involved in cell proliferation, differentiation, epithelial-mesenchymaltransitionand tissue remodeling. Bronchial biopsy specimens (BBs) were obtained from 7 healthy controls (HC)and 10 COPD and subjected to paraffin embedding; BBs from HC were also used for epithelial cell expansion andpHBEC/ALI (air-liquid interface) culture. pHBEC/ALI were exposed to cigarette smoke extract (CSE) for 7, 14and 21 days. In BBs, Oct4, CD146 and CD105 were evaluated by immunohistochemistry. In pHBEC/ALI, theexpression of Oct4, CD146, CD105 and acetyl-αtubulin was evaluated by Western Blot, MUC5AC and IL-8measurements by ELISA.The Oct4 epithelial immunoreactivity was lower in COPD than in HC, whilst CD146 and CD105 expression washigher in COPD than in HC. In pHBEC/ALI, Transepithelial Electrical Resistance values, measured over 7 to 21days of differentiation, decreased by 18% (2.5% CSE) and 29% (5% CSE) compared to untreated samples. Oct4and acetyl-αtubulin were induced after one-week differentiation and downregulated by CSE in reconstitutedepithelium; CD146, CD105, MUC5AC and IL-8 were increased by CSE.Oct4 de-regulation and CD146 and CD105 overexpression, induced by cigarette smoke exposure, might play arole in airway epithelial dysfunction by causing changes in self-renewal and mesenchymal transition mechanisms,leading to alteration of epithelium homeostasis and abnormal tissue remodeling involved in progression ofCOPD.
Lingua originaleEnglish
Numero di pagine8
RivistaLife Sciences
Stato di pubblicazionePublished - 2022

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.3000.3000???


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