Structure et pathologie des membranes basales.

Abstract

Basement membranes are thin layers of specialized extracellular matrix separating cells of different origins. They fulfill mechanical functions as a scaffolding for cells and tissues as well as biological functions such as filtration of salts and molecules and control of cellular behaviour. The complex composition of basement membranes has been elucidated to a large extent during the last 15 years. Collagen IV, laminin, nidogen and heparan sulfate proteoglycans are major specific and ubiquitous components. Several of these proteins represent families of isoforms, the expression of which is spatio-temporally regulated, providing a certain degree of polymorphism. In the skin, for example, additional components like collagen VII are associated with basement membranes. Constitutive molecules are assembled according to precise patterns into large polymers and complexes. Collagen IV and laminin can separately form large and stable polymeric networks considered as the scaffolding for anchoring cells and other basement membranes components. These two polymers are probably held together by nidogen which can develop high affinity interactions with both collagen IV and laminin. One can therefore predict that a molecular defect in one of these proteins could yield an abnormal supramolecular assembly of basement membranes and thus alterations in their biological and mechanical functions. Nature has provided us with some clues for this hypothesis in the form of diverse pathologies especially in kidneys and skin. In two renal diseases, Goodpasture and Alport syndromes, defects of collagen IV chains have been identified while several bullous diseases of the skin may have their origin in alterations of collagen VII and of a laminin variant.