Role of CD146 in bronchial epithelial differentiation and repair: implications for severe asthma - 09/05/26
, L. Moreno a, K. Valette a, b, A. Joshkon a, c, N. Bardin a, c, d, M. Blot-Chabaud a, c, P. Chanez a, b, D. Gras aRésumé |
Introduction |
Asthma is a chronic respiratory disease affecting nearly 300 million people worldwide, with 2–10% suffering from severe asthma. Bronchial epithelium dysfunction plays a central role in asthma pathophysiology. CD 146 , an adhesion molecule highly expressed in vascular cells, is also present in epithelial cells, although its functions in this context remain poorly understood. We previously reported that CD 146 is expressed by the bronchial epithelium and mainly by the basal cells. This study aimed to investigate the role of CD 146 in bronchial epithelium differentiation and repair, and its implication in severe asthma.
Methods |
Bronchial epithelia from healthy controls (C) and severe asthma (SA) patients were reconstituted in vitro using air-liquid interface culture. Undifferentiated bronchial epithelial cells ( n = 10 C; 6 SA) and CD 146− sorted cells ( n = 10 C; 5 SA) were followed during differentiation. In parallel, CD 146 expression was further assessed in differentiated epithelia ( n = 30 C; 26 SA). Then, CD 146 was silenced using lentiviral shRNA in undifferentiated bronchial epithelial cells and its effects were followed until obtention of a fully differentiated epithelium ( n = 2). Finally, to better understand the potential involvement of CD 146 in repair process, CD 146 expression kinetics were evaluated in a 14-day virus-induced exacerbation model ( n = 6 C; 6 SA).
Results |
Loss of CD 146 impaired epithelial differentiation, as evidenced by poorly differentiated epithelia reconstituted from CD 146− cells. In unsorted cultures, CD 146 expression decreased during differentiation (−70% from day 0 to day 28, p < 0.05), while shRNA-mediated silencing seems to confirm its role in this process. In severe asthma, CD 146 was significantly overexpressed at both mRNA (+219%, p < 0.0001) and protein (+34%, p < 0.05) levels in differentiated epithelium and differences in the differentiation has been observed. During a virus-induced exacerbation, CD 146 seems to be involved in the epithelium repair.
Conclusion |
Our findings identify CD 146 as a key regulator of bronchial epithelial differentiation and repair. Its overexpression in severe asthma highlights a potential contribution to disease pathophysiology and suggests CD 146 as a novel target for therapeutic investigation.
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Vol 43 - N° 1
P. 9 - mai 2026 Retour au numéro
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