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1 increases airway wound repair via MMP-2 up-regulation:A new pathway for epithelial wound repair?
1 Institut National de la Sante et de la Recherche Medicale, INSERM U651 (Faculte de Medecine, Universite Paris XII), Creteil, France; Service d'Anatomie Pathologie, CHU de Caen, Caen, France
2 Institut National de la Sante et de la Recherche Medicale, INSERM U651 (Faculte de Medecine, Universite Paris XII), Creteil, France; Service d'ORL et Chirurgie Cervico-Faciale, Hopital Henri Mondor ( AP-HP) et Hopital Intercommunal, Creteil, France
3 Institut National de la Sante et de la Recherche Medicale, INSERM U651 (Faculte de Medecine, Universite Paris XII), Creteil, France
4 Institut National de la Sante et de la Recherche Medicale, INSERM U651 (Faculte de Medecine, Universite Paris XII), Creteil, France; Service de Physiologie-Explorations Fonctionnelles, Hopital Henri Mondor (AP-HP), Creteil, France
5 Institut National de la Sante et de la Recherche Medicale, INSERM U651 (Faculte de Medecine, Universite Paris XII), Creteil, France; Departement de Genetique, cytogenetique et embryologie, Groupe Hospitalier Pitie-Salpetriere (AP-HP), Paris, France
* To whom correspondence should be addressed. E-mail: lechapt-e{at}chu-caen.fr.
In vivo, TGF-
1 and MMPs present at the site of airway injury are thought to contribute to epithelial wound repair. As TGF-1 can modulate MMP expression and MMPs play an important role in wound repair, we hypothesized that TGF-1 may enhance airway epithelial repair via MMPs secreted by epithelial cells. We evaluated the in vitro influence of TGF-1 on wound repair in human airway epithelial cells cultured under conditions allowing differentiation. The results showed that TGF-1 accelerated in vitro airway wound repair, whereas MMP inhibitors prevented this acceleration. In parallel, we examined the effect of TGF-1 on the expression of MMP-2 and MMP-9. TGF-1 induced a dramatic increase of MMP-2 expression with an increased steady-state level of MMP-2 mRNA, contrasting with a slight increase in MMP-9 expression. To confirm the role of MMP-2, we subsequently evaluated the effect of MMP-2 on in vitro airway wound repair and demonstrated that the addition of MMP-2 reproduced the acceleration of wound repair induced by TGF-1. These results strongly suggest that TGF-1 increases in vitro airway wound repair via MMP-2 up-regulation. It also raises the issue of a different in vivo biological role of MMP-2 and MMP-9 depending on the cytokine microenvironment.
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