MMP7 shedding of syndecan-1 facilitates re-epithelialization by affecting alpha(2)beta(1) integrin activation.
BACKGROUND
Lung injury promotes the expression of matrix metalloproteinase-7 (MMP7, matrilysin), which is required for neutrophil recruitment and re-epithelialization. MMP7 governs the lung inflammatory response through the shedding of syndecan-1. Because inflammation and repair are related events, we evaluated the role of syndecan-1 shedding in lung re-epithelialization.


RESULTS
Epithelial injury induced syndecan-1 shedding from wild-type epithelium but not from Mmp7(-/-) mice in vitro and in vivo. Moreover, cell migration and wound closure was enhanced by MMP7 shedding of syndecan-1. Additionally, we found that syndecan-1 augmented cell adhesion to collagen by controlling the affinity state of the alpha(2)beta(1) integrin.


CONCLUSIONS
MMP7 shedding of syndecan-1 facilitates wound closure by causing the alpha(2)beta(1) integrin to assume a less active conformation thereby removing restrictions to migration. MMP7 acts in the lungs to regulate inflammation and repair, and our data now show that both these functions are controlled through the shedding of syndecan-1.
Chen
Peter
P
Center for Lung Biology, Department of Medicine, University of Washington, Seattle, WA, USA. petechen@u.washington.edu
Abacherli
Laura E
LE
Nadler
Samuel T
ST
Wang
Ying
Y
Li
Qinglang
Q
Parks
William C
WC
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement; D004847:Epithelial Cells / Q000166:cytology; D055785:Gene Knockdown Techniques; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000201:enzymology*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D053668:Syndecan-1 / Q000378:metabolism* / Q000502:physiology
D038982:Integrin alpha2beta1; D053668:Syndecan-1; D020783:Matrix Metalloproteinase 7