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.
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.
Authors: Claudia Paret; Mehdi Bourouba; Alexander Beer; Kaoru Miyazaki; Martina Schnölzer; Sabine Fiedler; Margot Zöller Journal: Int J Cancer Date: 2005-07-10 Impact factor: 7.396
Authors: Pratima Nangia-Makker; Tirza Raz; Larry Tait; Victor Hogan; Rafael Fridman; Avraham Raz Journal: Cancer Res Date: 2007-12-15 Impact factor: 12.701
Authors: Steven T Sizemore; Gina M Sizemore; Christine N Booth; Cheryl L Thompson; Paula Silverman; Gurkan Bebek; Fadi W Abdul-Karim; Stefanie Avril; Ruth A Keri Journal: Breast Cancer Res Treat Date: 2014-05-22 Impact factor: 4.872
Authors: Jonas Elmwall; Jakub Kwiecinski; Manli Na; Abukar Ahmed Ali; Veronica Osla; Lindsey N Shaw; Wanzhong Wang; Karin Sävman; Elisabet Josefsson; Johan Bylund; Tao Jin; Amanda Welin; Anna Karlsson Journal: Infect Immun Date: 2017-06-20 Impact factor: 3.441
Authors: László Herszényi; Loránd Barabás; István Hritz; Gábor István; Zsolt Tulassay Journal: World J Gastroenterol Date: 2014-10-07 Impact factor: 5.742
Authors: Ruben Hummelen; Jean M Macklaim; Jordan E Bisanz; Jo-Anne Hammond; Amy McMillan; Rebecca Vongsa; David Koenig; Gregory B Gloor; Gregor Reid Journal: PLoS One Date: 2011-11-02 Impact factor: 3.240
Authors: László Herszényi; István Hritz; Gábor Lakatos; Mária Zsófia Varga; Zsolt Tulassay Journal: Int J Mol Sci Date: 2012-10-16 Impact factor: 5.923