title: Differential expression of matrix metalloproteinases and interleukin-8 during regeneration of human airway epithelium in vivo.
abstract: In many airway diseases, the airway epithelium is severely damaged and has to regenerate rapidly to restore its function. The regeneration process involves chronological steps of epithelial cell migration, proliferation, stratification, and differentiation. The present study has used an in vivo humanized airway xenograft model in nude mice that mimics the regeneration dynamics of human airway epithelium after severe injury, and human-specific molecular tools, to study the expression profiles of epithelial matrix metalloproteinases (MMPs)-7 and -9, of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and of the pro-inflammatory cytokine interleukin-8 (IL-8) during the different steps of human airway epithelium regeneration. It was found that during the cell migration and proliferation steps, airway epithelial cells expressed IL-8 at a high level, whereas airway epithelial pseudo-stratification and surface airway epithelial differentiation were associated with increased expression of MMPs and a progressive decrease in IL-8. Interestingly, immunohistochemical analysis revealed exclusive expression of MMPs at the apical part of the well-differentiated regenerated airway epithelium, and incubation of the regenerating epithelial cells with MMP inhibitors led to abnormal epithelial differentiation. These data provide new insight into the temporal expression of MMPs and IL-8 during the regeneration of airway epithelium and demonstrate the involvement of these factors during the different steps that lead to restoration of a well-differentiated and functional airway epithelium.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Mixte de Recherche Santé (UMR S) 514, Reims, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Coraux
authors.forename: Corinne
authors.initials: C
authors.lastname: Martinella-Catusse
authors.forename: Béatrice
authors.initials: B
authors.lastname: Nawrocki-Raby
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Hajj
authors.forename: Henriette
authors.initials: H
authors.lastname: Burlet
authors.forename: Sandie
authors.initials: S
authors.lastname: Escotte
authors.forename: Véronique
authors.initials: V
authors.lastname: Laplace
authors.forename: Philippe
authors.initials: P
authors.lastname: Birembaut
authors.forename: Edith
authors.initials: E
authors.lastname: Puchelle
mesh_terms: D000818:Animals; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D016209:Interleukin-8 / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration / Q000502:physiology*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D020782:Matrix Metalloproteinases; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9