title: Endothelial Cell Mediated Promotion of Ciliated Cell Differentiation of Human Airway Basal Cells via Insulin and Insulin-Like Growth Factor 1 Receptor Mediated Signaling.
abstract: Human airway basal cells (BC) function as stem/progenitor cells of the human airway epithelium, capable of differentiating into ciliated and secretory cells during turnover and repair. The positioning of BC along the basement membrane allows for potential paracrine signaling from non-epithelial cells in the mesenchyme to regulate BC function. Based on the knowledge that interaction between the airway epithelium and mesenchyme is critical for proper maintenance of both tissues, and that endothelial cells (EC) can regulate multiple functions of BC, the present study was designed to help understand the role of BC and EC cross-talk in regulating BC stem/progenitor function. Using an in vitro co-culture system that mimics the in vivo physical separation of these cell types, we assessed the impact of primary lung microvascular EC on differentiation of primary BC into a mucociliated epithelium. The data demonstrate that co-culture of BC and lung microvasculature EC results in increased ciliated cell differentiation of BC via activation of insulin (INS) and insulin-like growth factor 1 (IGF1) receptor (INSR and IGF1R) mediated signaling in BC. Consistent with this data, siRNA mediated knockdown of INSR and IGF1R in BC suppressed ciliated cell differentiation. Together these findings identify an important signaling pathway required for differentiation of BC into a ciliated cells and demonstrate the importance of BC-EC cross-talk in regulating normal airway epithelial structure.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 164, New York, NY, 10065, USA.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Gomi
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 164, New York, NY, 10065, USA.
authors.forename: Yongjiang
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 164, New York, NY, 10065, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Arbelaez
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 164, New York, NY, 10065, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, 1300 York Avenue, Box 164, New York, NY, 10065, USA. geneticmedicine@med.cornell.edu.|Pulmonary, Critical Care & Sleep Medicine, Department of Medicine, University of Oklahoma Health Sciences Center, 800 N. Research Parkway, Building 800, 4th Floor, Rm 410, Oklahoma City, OK, 73104, USA. geneticmedicine@med.cornell.edu.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Walters
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000166:cytology; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D002923:Cilia; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008168:Lung / Q000166:cytology; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
chemical_list: D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin
keywords: Basal stem/progenitor cells; Ciliated cells; Differentiation; Endothelial cells; Human airway epithelium; Insulin; Insulin-like growth factor 1; Signaling