Échange d’informations entre cellules et matrice extracellulaire Influence du vieillissement

Information exchanges between cells and extracellular matrix. Influence of aging

Laboratoire de Recherche Ophtalmologique, Hôtel-Dieu, Université Paris 5, 1 place du Parvis Notre-Dame, 75004 Paris, France

Auteur correspondant : Jacqueline Labat-Robert, lrobert5@wanadoo.fr

Reçu : 18 Janvier 2012

Résumé

Depuis plusieurs années, nous sommes concernés par le vieillissement des populations et les maladies qui l’accompagnent. Nombre de ces dernières concernent les tissus conjonctifs. C’est ce qui motive notre intérêt pour l’étude du comportement de la matrice et des récepteurs au cours du vieillissement. Nous avons suivi l’évolution de la fibronectine, de son principal récepteur au cours du vieillissement chronologique mais aussi au cours du vieillissement photo-induit. La fibronectine est souvent fragmentée au cours de ces maladies. Ses fragments possèdent des propriétés dont la molécule mère est dépourvue (matricryptines). Ceci a ouvert un nouveau champ d’investigation prometteur. La récente découverte de l’élasticité de la fibronectine ouvre aussi de nouvelles perspectives dans le dialogue cellules-matrice.

Abstract

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.