This Article Full Text Full Text (PDF) All Versions of this Article: 2006-0270OCv1 36/3/296    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by LeSimple, P. Articles by Puchelle, E. Search for Related Content PubMed PubMed Citation Articles by LeSimple, P. Articles by Puchelle, E.

Trefoil Factor Family 3 Peptide Promotes Human Airway Epithelial Ciliated Cell Differentiation

INSERM U514, Université Reims Champagne Ardenne, and CHU Reims, Hôpital Maison Blanche, Reims; INSERM U560, Lille, France; Otto-von-Guericke-Universität, Institut für Molekularbiologie und Medizinische Chemie, Magdeburg, Germany; and Washington University School of Medicine, St. Louis, Missouri

Correspondence and requests for reprints should be addressed to Edith Puchelle, INSERM U514, 45 rue Cognacq Jay, F-51092 Reims Cedex, France. E-mail: edith.puchelle{at}univ-reims.fr

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 -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 -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.

Key Words: airway epithelium • ciliated cell differentiation • TFF3 • mucins • FOXJ1

CLINICAL RELEVANCE Our study demonstrates for the first time that TFF3 peptide is able to increase ciliated cell differentiation in human airway epithelium, thus participating in restoration of epithelial defense functions.