Distinctive functions of membrane type 1 matrix-metalloprotease (MT1-MMP or MMP-14) in lung and submandibular gland development are independent of its role in pro-MMP-2 activation
Distinctive functions of membrane type 1 matrix-metalloprotease (MT1-MMP or MMP-14) in lung and submandibular gland development are independent of its role in pro-MMP-2 activation
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DOI：
10.1016/j.ydbio.2004.09.033
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发表时间：
2005-01-01
影响因子：
2.7
通讯作者：
Apte, SS
中科院分区：
文献类型：
--
作者：
Oblander, SA;Zhou, ZJ;Apte, SS
膜1型基质金属蛋白酶（MT 1-MMP或MMP-14）是pro-MMP-2的主要激活剂，对骨骼发育至关重要。我们在这里表明，它是所需的分支形态发生的下颌下腺，但不是肺。相反，在肺中，它对出生后肺泡隔的发育至关重要。Mmp 14-/-小鼠的肺发育在肺泡前阶段被阻止，伴随着未成熟球囊的代偿性过度膨胀。Mmp 2-/-小鼠在肺和下颌下腺中缺乏类似的缺陷，这表明NIT 1-MMP通过独立于pro-MMP-2激活的机制起作用。由于肺中的发育缺陷在初始血管化（E16.5）的时间前后首次显现，因此我们研究了来自Mmp 14 +/+和Mmp 14-/-小鼠的肺内皮细胞的行为。来自1周龄Mmp 14-/-小鼠肺的内皮细胞显示出在Matrigel上减少的迁移和三维结构的形成。由于肺间隔发育需要毛细血管生长，Mmp 14-/-小鼠肺发育不全的潜在机制可能是血管生成缺陷，支持血管生成是肺实质肿块获取的关键限速步骤的模型。(C)2004年爱思唯尔公司All rights reserved.
Membrane type 1-matrix metalloprotease (MT1-MMP or MMP-14) is a major activator of pro-MMP-2 and is essential for skeletal development. We show here that it is required for branching morphogenesis of the submandibular gland but not the lung. Instead, in the lung, it is essential for postnatal development of alveolar septae. Lung development in Mmp14-/- mice is arrested at the prealveolar stage with compensatory hyperinflation of immature saccules. Mmp2-/- mice lacked comparable defects in the lung and submandibular gland, suggesting that NIT1-MMP acts via mechanisms independent of pro-MMP-2 activation. Since the developmental defects in the lung are first manifest around the time of initial vascularization (E16.5), we investigated the behavior of pulmonary endothelial cells from Mmp14+/+ and Mmp14-/- mice. Endothelial cells from lungs of 1-week-old Mmp14-/- mice show reduced migration and formation of three-dimensional structures on Matrigel. Since pulmonary septal development requires capillary growth, the underlying mechanism of pulmonary hypoplasia in Mmp14-/- mice may be defective angiogenesis, supporting a model in which angiogenesis is a critical rate-limiting step for acquisition of pulmonary parenchymal mass. (C) 2004 Elsevier Inc. All rights reserved.