title: Trefoil factor family 3 peptide promotes human airway epithelial ciliated cell differentiation.
abstract: Human airway surface epithelium is frequently damaged by inhaled factors (viruses, bacteria, xenobiotic substances) as well as by inflammatory mediators that contribute to the shedding of surface epithelial cells. To regain its protective function, the epithelium must rapidly repair and redifferentiate. The Trefoil Factor Family (TFF) peptides are secretory products of many mucous cells. TFF3, the major TFF in the airways, is able to enhance airway epithelial cell migration, but the role of this protein in differentiation has not been defined. To identify the specific role of TFF3 in the differentiation of the human airway surface epithelium, we analyzed the temporal expression pattern of TFF3, MUC5AC, and MUC5B mucins (goblet cells) and ciliated cell markers beta-tubulin (cilia) and FOXJ1 (ciliogenesis) during human airway epithelial regeneration using in vivo humanized airway xenograft and in vitro air-liquid interface (ALI) culture models. We observed that TFF3, MUC5AC, MUC5B, and ciliated cell markers were expressed in well-differentiated airway epithelium. The addition of exogenous recombinant human TFF3 to epithelial cell cultures before the initiation of differentiation resulted in no change in MUC5AC or cytokeratin 13 (CK13, basal cell marker)-positive cells, but induced an increase in the number of FOXJ1-positive cells and in the number of beta-tubulin-positive ciliated cells (P < 0.05). Furthermore, this effect on ciliated cell differentiation could be reversed by specific epidermal growth factor (EGF) receptor (EGF-R) inhibition. These results indicate that TFF3 is able to induce ciliogenesis and to promote airway epithelial ciliated cell differentiation, in part through an EGF-R-dependent pathway.
authors.affiliation: INSERM U514, Université Reims Champagne Ardenne, and CHU Reims, Hôpital Maison Blanche, Reims, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: LeSimple
authors.forename: Isabelle
authors.initials: I
authors.lastname: van Seuningen
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Buisine
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Copin
authors.forename: Margitta
authors.initials: M
authors.lastname: Hinz
authors.forename: Werner
authors.initials: W
authors.lastname: Hoffmann
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Hajj
authors.forename: Steven L
authors.initials: SL
authors.lastname: Brody
authors.forename: Christelle
authors.initials: C
authors.lastname: Coraux
authors.forename: Edith
authors.initials: E
authors.lastname: Puchelle
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002923:Cilia / Q000648:ultrastructure; D004847:Epithelial Cells / Q000166:cytology* / Q000637:transplantation / Q000648:ultrastructure; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009077:Mucins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics* / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D012137:Respiratory System / Q000166:cytology* / Q000648:ultrastructure; D015398:Signal Transduction; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D000071165:Trefoil Factor-3
chemical_list: D009077:Mucins; D010455:Peptides; D012333:RNA, Messenger; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; D066246:ErbB Receptors