title: Activation of MMP-2 by Clostridium difficile toxin B in bovine smooth muscle cells.
abstract: Matrix metalloproteinase-2 (MMP-2) plays critical roles in cell migration through the breakdown of the extracellular matrix. Cell movements require dynamic actin reorganization, which is controlled by Rho family GTPases. In order to examine the relation between MMP-2 regulation and actin reorganization, we used several inhibitors of Rho family GTPases. Treatment of smooth muscle cells with Clostridium difficile toxin B known to inactivate Rho family GTPases activated MMP-2. However, neither C3 transferase, a Rho inhibitor, nor Y-27632, a specific inhibitor of Rho-kinase, induced MMP-2 activation. Treatment with C3 transferase and Y-27632 caused morphological changes into the round and stellate shape, respectively, by inhibition of actin stress fiber formation. In addition, toxin B treatment induced expression and processing of MT1-MMP, a major activator of MMP-2. Taken together, we suggest the involvement of Rho family GTPases, although inhibition of neither Rho nor Rho-kinase is sufficient, in the activation of MMP-2 through expression and activation of MT1-MMP.
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Koike
authors.forename: M
authors.initials: M
authors.lastname: Kuzuya
authors.forename: T
authors.initials: T
authors.lastname: Asai
authors.forename: S
authors.initials: S
authors.lastname: Kanda
authors.forename: X W
authors.initials: XW
authors.lastname: Cheng
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Banno
authors.forename: Y
authors.initials: Y
authors.lastname: Nozawa
authors.forename: A
authors.initials: A
authors.lastname: Iguchi
mesh_terms: D036002:ADP Ribose Transferases / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology*; D015153:Blotting, Western; D001905:Botulinum Toxins; D002417:Cattle; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D016360:Clostridioides difficile; D015638:Cytochalasin D / Q000494:pharmacology; D003603:Cytotoxins / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D011725:Pyridines / Q000494:pharmacology; D022502:Stress Fibers / Q000187:drug effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000577:Amides; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D011725:Pyridines; D019715:Tissue Inhibitor of Metalloproteinase-1; C031815:toxB protein, Clostridium difficile; D019716:Tissue Inhibitor of Metalloproteinase-2; C108830:Y 27632; D015638:Cytochalasin D; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins