Labat-Robert Jacqueline
Laboratoire de Recherche Ophtalmologique, Hôtel-Dieu, Université Paris 5, Paris, France.
Biol Aujourdhui. 2012;206(2):103-9. doi: 10.1051/jbio/2012012. Epub 2012 Jul 4.
Our interest, since a number of years, has focalized on the worldwide rapid expansion of the aging population, accompanied by a progressive increase of age-related pathologies. Most of these concern connective tissues, that are rich in extracellular matrix (ECM), such as osteoarticular, cardiovascular and pulmonary diseases. Therefore age-related modifications of connective tissues become of increasing importance for the understanding of these diseases. In this article, we shall recapitulate some of our (and others') experiments on fibronectin, an important matrix glycoprotein mediating cell-matrix interactions. We studied the effect of age on fibronectin biosynthesis and also the effect of UV-radiation. Both conditions, age and radiation, produce a significant increase of fibronectin biosynthesis. Some results, when in vitro aging of skin fibroblasts was studied, exhibited also a passage-dependent regulation of fibronectin biosynthesis. A few studies, quoted in this review, were reported about the effect of age on integrin expression and function. An important finding was that novel biological fragments of fibronectin have proteolytic activities, pro-inflammatory activity in articular tissues, enhance malignant transformation as well as other activities. Proteolytic activity also increases with age-dependent increase of fibronectin fragmentation. This process exhibits positive feedback properties, forming a vicious circle, possibly important for the age-dependent aggravation of connective tissue diseases. Besides these observations, the recent demonstration of fibronectin elasticity suggests its implication in novel biological regulation as for instance mechano-transduction.
多年来，我们一直关注全球老龄人口的迅速增长，以及与之相伴的与年龄相关疾病的不断增加。其中大多数疾病涉及富含细胞外基质（ECM）的结缔组织，如骨关节疾病、心血管疾病和肺部疾病。因此，结缔组织与年龄相关的变化对于理解这些疾病变得越来越重要。在本文中，我们将概述一些我们（以及其他人）关于纤连蛋白的实验，纤连蛋白是一种介导细胞-基质相互作用的重要基质糖蛋白。我们研究了年龄对纤连蛋白生物合成的影响以及紫外线辐射的影响。年龄和辐射这两种条件都会使纤连蛋白的生物合成显著增加。在研究皮肤成纤维细胞的体外老化时，一些结果还显示了纤连蛋白生物合成的传代依赖性调节。本综述引用的一些研究报道了年龄对整合素表达和功能的影响。一个重要发现是，纤连蛋白的新型生物片段具有蛋白水解活性、关节组织中的促炎活性、促进恶性转化以及其他活性。蛋白水解活性也随着纤连蛋白片段化的年龄依赖性增加而增加。这个过程表现出正反馈特性，形成一个恶性循环，这可能对结缔组织疾病的年龄依赖性加重很重要。除了这些观察结果，最近对纤连蛋白弹性的证明表明它参与了新的生物调节，例如机械转导。
