Imbalance of Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 is Associated with Pulmonary Emphysema in Klotho Mice

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Klotho mice, which exhibit multiple phenotypes resembling human aging, developpulmonary emphysema. In this study, to clarify the mechanism of their emphysematouschange through development, we evaluated the expression of matrix metalloproteinase(MMP)-2, 9 and the tissue inhibitors of matrix metalloproteinase (TIMP)-1, 2 in thelungs of Klotho mice and wild type mice. Klotho mice showed obvious air spaceenlargement at 5 weeks of age, but not at 2 weeks of age. Immunohistochemical analysisrevealed that expression of MMP-9 was increased in Klotho mice compared with wildtype at 5 weeks of age. Western blot analysis and gelatin zymography also revealed thatthe expression and the gelatinolytic activity of MMP-9 were increased in the lungs ofKlotho mice. The expression of TIMP-1 decreased in the lungs of Klotho mice. MMP-2and TIMP-2 showed no significant differences at 5 weeks of age. At 2 weeks of age, therewere no significant differences in the expressions of MMP-9 and TIMP-1 betweenKlotho and wild type mice. These findings suggest that imbalance of MMP-9 andTIMP-1 is associated with the development of pulmonary emphysema in Klotho mice.
神戸大学の論文