title: Impaired alveolization in mice deficient in membrane-type matrix metalloproteinase 1 (MT1-MMP).
abstract: To clarify the involvement of membrane-type matrix metalloproteinase 1 (MT1-MMP) in lung organogenesis, we studied the lung morphology of 13-day-old MT1-MMP null mice. The lung architecture in MT1-MMP null mice was abnormal, and the airspace compartments were characterized by smooth walls and larger size. Most of the compartment wall consisted of one or two layers of cells and interstitial connective tissue that was thicker than that of normal alveoli. The wall frequently had capillaries on both sides of the interstitial connective tissue. These findings indicate that the lung in MT1-MMP null mice at 13 days of age is comparable to that of neonatal mice, i.e., it represents the stage before alveolization, suggesting that the generation of a large respiratory surface - the final process of lung development - is impaired in MT1-MMP null mice. Moreover, a zymography assay revealed decreased activity of matrix metalloproteinase 2 (MMP-2) in MT1-MMP null mice, suggesting that activation of pro-MMP-2 by MT1-MMP is critical in this process.
authors.affiliation: Department of Oral Anatomy, Health Sciences University of Hokkaido School of Dentistry, Ishikari-Tobetsu, Japan. irie@hoku-iryo-u.ac.jp
authors.forename: Kazuharu
authors.initials: K
authors.lastname: Irie
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Komori
authors.forename: Motoharu
authors.initials: M
authors.lastname: Seiki
authors.forename: Eichi
authors.initials: E
authors.lastname: Tsuruga
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sakakura
authors.forename: Tohru
authors.initials: T
authors.lastname: Kaku
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yajima
mesh_terms: D000818:Animals; D015536:Down-Regulation; D053511:Matrix Metalloproteinase 14; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D038081:Organogenesis / Q000235:genetics; D011650:Pulmonary Alveoli / Q000201:enzymology* / Q000254:growth & development* / Q000648:ultrastructure
chemical_list: C507096:Mmp14 protein, mouse; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D053511:Matrix Metalloproteinase 14