Fibroblast-myofibroblast transition is differentially regulated by bronchial epithelial cells from asthmatic XXXX .

@entity1 @entity565 @entity1970 @entity6474 @entity15263
BACKGROUND: Airway remodeling is a proposed mechanism that underlies the persistent loss of lung function associated with childhood @entity565 . Previous studies have demonstrated that @entity1 lung fibroblasts (HLFs) co-cultured with primary @entity1 bronchial epithelial cells (BECs) from asthmatic @entity1 exhibit greater expression of extracellular matrix (ECM) components compared to co-culture with BECs derived from healthy @entity1 . Myofibroblasts represent a population of differentiated fibroblasts that have greater synthetic activity. We hypothesized co-culture with asthmatic BECs would lead to greater fibroblast to myofibroblast transition (FMT) compared to co-culture with healthy BECs. METHODS: BECs were obtained from well-characterized asthmatic and healthy @entity1 and were proliferated and differentiated at an air-liquid interface (ALI). BEC-ALI cultures were co-cultured with HLFs for 96  hours. RT-PCR was performed in HLFs for @entity1970 ( @entity1970 ) and flow cytometry was used to assay for @entity1970 antibody labeling of HLFs. RT-PCR was also preformed for the expression of tropomyosin-I as an additional marker of myofibroblast phenotype. In separate experiments, we investigated the role of @entity6474 in BEC- @entity15263 co-cultures using monoclonal antibody inhibition. RESULTS: Expression of @entity1970 by HLFs alone was greater than by HLFs co-cultured with healthy BECs, but not different than @entity1970 expression by HLFs co-cultured with asthmatic BECs. Flow cytometry also revealed significantly less @entity1970 expression by healthy co-co-cultures compared to asthmatic co-cultures or @entity15263 alone. Monoclonal antibody inhibition of @entity6474 led to similar expression of @entity1970 between healthy and asthmatic BEC- @entity15263 co-cultures. Expression of topomyosin-I was also significantly increased in @entity15263 co-cultured with asthmatic BECs compared to healthy BEC- @entity15263 co-cultures or @entity15263 cultured alone. CONCLUSION: These findings suggest dysregulation of FMT in @entity15263 co-cultured with asthmatic as compared to healthy BECs. Our results suggest @entity6474 may be involved in the differential regulation of FMT by asthmatic BECs. These findings further illustrate the importance of BEC- @entity15263 cross-talk in asthmatic airway remodeling.
