Anti-alpha2 integrin antibody induces secretion and activation of 72-kDa progelatinase by human fibroblasts.
We examined the effects of the extracellular matrix proteins fibronectin, laminin, and matrigel on 72-kDa progelatinase secretion by human lip fibroblasts (KD) and skin fibroblasts (MRC9 and HSF). By gelatin zymography, 1.7 +/- 0.2-fold, 1.7 +/- 0.2-fold, and 1.8 +/- 0.3-fold increases were observed in 72-kDa progelatinase secretion from KD cells treated with fibronectin, laminin, and matrigel, respectively. Laminin and matrigel, but not fibronectin, stimulated 72-kDa progelatinase secretion from HSF cells. Fibronectin, laminin, and matrigel did not stimulate 72-kDa progelatinase secretion by MRC9 cells. Anti-alpha2 integrin antibody-stimulated 72-kDa progelatinase secretion and induced the 62-kDa activated form of 72-kDa progelatinase by KD cells. Activated p42 MAP kinase (MAPK) expression was down-regulated by anti-alpha2 integrin antibody. Anti-alpha2 integrin antibody stimulated 72-kDa progelatinase secretion by HSF cells without inducing the 62-kDa activated form. The data suggest that interaction between fibroblasts and extracellular matrix components via alpha2 integrin plays an important role in regulating secretion and activation of 72-kDa gelatinase and that down-regulation of activated p42 MAPK may be involved in the 72-kDa progelatinase activation mechanism.
Ishibashi
Y
Y
Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Japan.
Ito
H
H
Seyama
Y
Y
Kubota
S
S
D000906:Antibodies / Q000494:pharmacology*; D015703:Antigens, CD / Q000032:analysis / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D003094:Collagen / Q000494:pharmacology; D004338:Drug Combinations; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D005353:Fibronectins / Q000494:pharmacology; D005434:Flow Cytometry / Q000379:methods; D018093:Gelatinases / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D039421:Integrin alpha2; D007700:Kinetics; D007797:Laminin / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000906:Antibodies; D015703:Antigens, CD; D004338:Drug Combinations; D004792:Enzyme Precursors; D005353:Fibronectins; D039421:Integrin alpha2; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D003094:Collagen; D019950:Mitogen-Activated Protein Kinase 1; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase