title: Increased matrix metalloproteinase-2 activity induced by TGF-beta 1 in duct cells of human salivary gland is associated with the development of cyst formation in vivo.
abstract: Proteolytic enzyme activity has been shown to be important for cyst formation. In this study, we constructed a cyst-like structure in vivo and analyzed molecular mechanisms involved in the development of the lesion. When SV40-immortalized duct cells of normal human salivary gland (NS-SV-DC) were treated with TGF-beta 1 at a concentration of 1 ng/ml or 5 ng/ml followed by co-inoculation with Matrigel into the backs of nude mice, they formed large cysts containing fluid when 5 ng/ml of TGF-beta 1 was used. Analysis of the fluid demonstrated high MMP activity. Immunohistochemical staining exhibited strong reactivity with anti-MMP-2 antibody in TGF-beta 1 (5 ng/ml)-treated NS-SV-DC. Northern blot analysis indicated that the expression of TGF-beta 1 and MMP-2 mRNAs in cells was greatly enhanced by treatment with 5 ng/ml TGF-beta 1. These findings suggest that the in vivo cyst formation by TGF-beta 1-treated cells is associated with continuous induction of MMP-2 activity.
authors.affiliation: Second Department of Orai and Maxillofacial Surgery, Tokushima University School of Dentistry, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Azuma
authors.forename: T
authors.initials: T
authors.lastname: Tamatani
authors.forename: T
authors.initials: T
authors.lastname: Yuki
authors.forename: K
authors.initials: K
authors.lastname: Motegl
authors.forename: M O
authors.initials: MO
authors.lastname: Hoque
authors.forename: H
authors.initials: H
authors.lastname: Yoshida
authors.forename: M
authors.initials: M
authors.lastname: Sato
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D003094:Collagen; D004396:Coloring Agents; D003560:Cysts / Q000201:enzymology / Q000209:etiology*; D004338:Drug Combinations; D005109:Extracellular Matrix; D005260:Female; D018093:Gelatinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin; D020778:Matrix Metalloproteinase 2; D061965:Matrix Metalloproteinase Inhibitors; D008666:Metalloendopeptidases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008967:Molecular Biology; D011480:Protease Inhibitors / Q000032:analysis / Q000378:metabolism; D011509:Proteoglycans; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018987:Salivary Ducts / Q000201:enzymology* / Q000473:pathology; D012466:Salivary Gland Diseases / Q000201:enzymology / Q000209:etiology; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*
chemical_list: D004396:Coloring Agents; D004338:Drug Combinations; D006023:Glycoproteins; D007797:Laminin; D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D011509:Proteoglycans; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D016212:Transforming Growth Factor beta; C059485:matrigel; D003094:Collagen; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2