Transforming growth factor-beta1 increases airway wound repair via MMP-2 upregulation: a new pathway for epithelial wound repair?
In vivo, transforming growth factor (TGF)-beta1 and matrix metalloproteinases (MMPs) present at the site of airway injury are thought to contribute to epithelial wound repair. As TGF-beta1 can modulate MMP expression and MMPs play an important role in wound repair, we hypothesized that TGF-beta1 may enhance airway epithelial repair via MMPs secreted by epithelial cells. We evaluated the in vitro influence of TGF-beta1 on wound repair in human airway epithelial cells cultured under conditions allowing differentiation. The results showed that TGF-beta1 accelerated in vitro airway wound repair, whereas MMP inhibitors prevented this acceleration. In parallel, we examined the effect of TGF-beta1 on the expression of MMP-2 and MMP-9. TGF-beta1 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-beta1. These results strongly suggest that TGF-beta1 increases in vitro airway wound repair via MMP-2 upregulation. It also raises the issue of a different in vivo biological role of MMP-2 and MMP-9 depending on the cytokine microenvironment.
Lechapt-Zalcman
E
E
INSERM U651, Faculty of Medicine, University Paris XII, Créteil, France. lechapt-e@chu-caen.fr
Prulière-Escabasse
V
V
Advenier
D
D
Galiacy
S
S
Charrière-Bertrand
C
C
Coste
A
A
Harf
A
A
d'Ortho
M-P
MP
Escudier
E
E
D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000502:physiology*
C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2