Age-dependent remodeling of connective tissue: role of fibronectin and laminin
Age-dependent remodeling of connective tissue: role of fibronectin and laminin
复制标题
DOI：
10.1016/j.patbio.2003.09.006
复制
发表时间：
2003-12-01
影响因子：
--
通讯作者：
Labat-Robert, J
中科院分区：
文献类型：
--
作者：
Labat-Robert, J
结缔组织与其他组织的不同之处在于其更丰富的细胞外基质（ECM）。该基质由相对大量的大分子组成，这些大分子之间以及它们周围的细胞相互作用。这些细胞、成纤维细胞、软骨细胞和其他细胞根据遗传和环境调节的“程序”分泌ECM大分子。最近发现，一种大分子相互作用的特征是某些 ECM 成分的选择性裂解。其中一些蛋白水解产物被证明具有母体分子所不具备的显着生物活性。这些机制被证明在衰老过程中发挥着重要作用。此类肽及其活性也称为基质隐蛋白，是由几种基质成分产生的。特别令人感兴趣的是这些源自纤连蛋白、层粘连蛋白和弹性蛋白的基质隐蛋白。它们通过对原始 ECM 成分进行蛋白水解攻击而产生，随后产生新的生物活性，在某些情况下形成自动放大的恶性循环。这种“表观遗传”、翻译后机制不是在基因组中编码的，它们既不是“偶然的”，也不是“混乱的”，而是非常可预测的，是“基质隐”位点的几个 ECM 成分中存在的结果，以及携带这些位点的基质成分和产生基质隐蛋白的蛋白水解酶的共同调节合成的结果。我们将讨论一些例子，这些例子来自我们实验室和其他实验室多年来进行的实验，涉及衰老和一些与年龄相关的病理学。 (C) 2003 年科学与医学版 Elsevier SAS。版权所有。
Connective tissues differ from other tissues in their more abundant extracellular matrix (ECM). This matrix is composed of a relatively large number of macromolecules interacting with each other as well as with the cells they are surrounding. Such cells, fibroblasts, chondrocytes and others, secrete the macromolecules of ECM according to a genetically and environmentally regulated "program". It appeared recently that one type of macromolecular interactions is characterized by the selective cleavage of some of the ECM components. Some of these proteolytic cleavage products were shown to possess remarkable biological activities absent from the parent molecules. Such mechanisms were shown to play an important role in aging processes. Also called matricryptins such peptides and their activities are produced from several matrix components. Of special interest are these matricryptins which are derived from fibronectin, laminin and elastin. Their production by proteolytic attack of the original ECM components, followed by their novel biological activities, form in some instances autoamplifying vicious circles. Such "epigenetic", post-translational mechanisms are not coded in the genome, they are neither "accidental", nor "chaotic" but remarkably predictable, the result of the presence in several ECM components of "matricryptic" sites and coregulated synthesis of matrix components carrying such sites and of proteolytic enzymes producing the matricryptins. Some examples will be discussed, derived from the experiments carried out in our laboratory and others over the years, involved in aging and in some of the age-dependent pathologies. (C) 2003 Editions scientifiques et medicales Elsevier SAS. All rights reserved.