Matrilysin-1 (MMP7) cleaves galectin-3 and inhibits wound healing in intestinal epithelial cells.
BACKGROUND
Galectin-3 is an animal lectin that has been implicated in wound healing and is decreased in inflammatory bowel disease (IBD). Matrix metalloproteinase-7 (MMP7), also known as matrilysin-1, a protease shown to cleave extracellular matrix proteins, is highly expressed in IBD tissues, especially at the leading edge of gastrointestinal ulcers. The ability of MMP7 to cleave galectin-3 and influence wound healing has not been reported previously. The aim was to determine whether MMP7 cleaves galectin-3 and modulates wound healing in intestinal epithelial cells.


METHODS
The cleaved fragments of galectin-3 were identified by N-terminal sequencing and mass spectrometry. Western blotting was used to detect the cleaved galectin-3 products in a colonic epithelial cell line (T84 cells). Cell migration was studied by the in vitro scratch method.


RESULTS
We demonstrate for the first time that MMP7 cleaves galectin-3 in vitro, resulting in three cleaved fragments (20.2 kDa, 18.9 kDa, and 15.5 kDa). Exogenous treatment of T84 cells with recombinant MMP7 resulted in the appearance of secreted galectin-3 cleavage fragments in the supernatant. MMP7 inhibited cell migration and resulted in wound retraction and the addition of MMP7 to galectin-3 abrogated the wound healing and cell migration induced by galectin-3.


CONCLUSIONS
We have demonstrated that galectin-3 is a substrate for MMP7. Cleavage of galectin-3 may be one mechanism by which MMP7 inhibits wound healing. This study has significance in understanding delayed wound healing in chronic intestinal diseases like intestinal ulcers and IBD, where MMP7 protein expression is elevated with a decreased galectin-3 protein expression.
Puthenedam
Manjula
M
Department of Medicine, Division of Gastroenterology, Johns Hopkins University, Baltimore, Maryland, USA.
Wu
Feng
F
Shetye
Alysha
A
Michaels
Alex
A
Rhee
Ki-Jong
KJ
Kwon
John H
JH
D002465:Cell Movement; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014945:Wound Healing
D037502:Galectin 3; D020783:Matrix Metalloproteinase 7
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