Matrix metalloproteases in aberrant fibrotic tissue remodeling.
Matrix metalloproteases in aberrant fibrotic tissue remodeling.
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DOI：
10.1513/pats.200601-012tk
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发表时间：
2006-06-01
期刊：
影响因子：
--
通讯作者：
Selman, Moises
中科院分区：
文献类型：
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作者：
Pardo, Annie;Selman, Moises
肺纤维化是多种间质性肺疾病的最终结果，其特征是细胞外基质(ECM)的异常重构，并严重扰乱了正常的肺结构。这种重塑包括细胞外基质成分在间质和肺泡腔的过度聚集和基底膜的破坏。长期以来，基质金属蛋白酶(MMPs)在肺纤维化的发病机制中起着重要作用，但其确切机制尚不清楚。在人类和实验性肺纤维化中，几种MMPs强烈上调，突显了肺内瘢痕形成的动态性质。MMPs能够共同切割细胞外基质和基底膜的所有成分，但重要的是，它们还处理生物活性介质，如生长因子、细胞因子、趋化因子和细胞表面受体。此外，它们还参与了影响更广泛底物的蛋白酶级联反应的启动。因此，MMPs可能在纤维化中观察到的几个相互关联的过程中发挥核心作用，如ECM重塑、基底膜破裂、上皮细胞凋亡、细胞迁移和血管生成。
Pulmonary fibrosis, the final result of a large variety of interstitial lung diseases, is characterized by an aberrant remodeling of extracellular matrix (ECM) with a profound disturbance of the normal lung architecture. This remodeling includes the exaggerated accumulation of ECM components in the interstitial and alveolar spaces and the disruption of the basement membranes. It has long been accepted that matrix metalloproteases (MMPs) play an important role in the pathogenesis of pulmonary fibrosis, but the exact mechanisms are not well characterized. Several MMPs are strongly up-regulated in human and experimental lung fibrosis, highlighting the dynamic nature of scarring within the lung. MMPs are collectively capable of cleaving all components of the ECM and basement membranes, but importantly, they also process bioactive mediators such as growth factors, cytokines, chemokines, and cell-surface receptors. Moreover, they participate in the initiation of proteinase cascades that impact much broader substrates. Consequently, MMPs may play a central role in several interrelated processes observed in fibrosis such as ECM remodeling, basement-membrane breakdown, epithelial-cell apoptosis, cell migration, and angiogenesis.