Impaired alveolization in mice deficient in membrane-type matrix metalloproteinase 1 (MT1-MMP)
Impaired alveolization in mice deficient in membrane-type matrix metalloproteinase 1 (MT1-MMP)
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DOI：
10.1007/s00795-004-0277-9
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发表时间：
2005-03-05
影响因子：
1.8
通讯作者：
Yajima, Toshihiko
中科院分区：
文献类型：
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作者：
Irie, Kazuharu;Komori, Kiyoshi;Yajima, Toshihiko
为了阐明膜型基质金属蛋白酶1 （MT1-MMP）在肺器官发生中的作用，我们研究了13日龄MT1-MMP缺失小鼠的肺形态。MT1-MMP缺失小鼠肺结构异常，肺腔壁光滑，体积较大。大部分肺泡壁由一层或两层细胞和间质结缔组织组成，比正常肺泡壁厚。壁间质结缔组织两侧常有毛细血管。这些发现表明，13日龄MT1-MMP缺失小鼠的肺与新生小鼠的肺相当，即它代表肺泡形成之前的阶段，这表明MT1-MMP缺失小鼠肺发育的最终过程——大呼吸表面的产生受到损害。此外，酶谱分析显示，MT1-MMP缺失小鼠的基质金属蛋白酶2 （MMP-2）活性降低，这表明MT1-MMP对MMP-2前的激活在这一过程中至关重要。
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.