Localization of extracellular matrix components in congenital nephrotic syndromes

While renal tissue from one fetus and a newborn with congenital nephrotic syndrome, Finnish type (FCNS), showed a normal basement membrane (BM) localization and composition, in another type of congenital nephrotic syndrome, diffuse mesangial sclerosis (DMS), most glomeruli demonstrated a completely disorganized matrix. In the latter, hyalinized glomerular segments were composed of irregular deposits of interstitial collagens I, III, V, and extensive deposits of heparin sulphate proteoglycan (HSPG), while collagen IV and laminin were completely absent in those areas. Apart from these sclerosed glomerular areas, normal capillarly loops revealed a matrix composition that was comparable to normal glomeruli. The additional immunolocalization of various extracellular matrix components during the development of normal human glomeruli revealed some significant age-dependent changes both in the localization of interstitial collagens and BM components: interstitial collagens I and III disappeared after the first S-shaped indentations appeared, while the interstitial collagen V remained along the glomerular BM and within the mesangium. The BM components showed no significant qualitative changes, but quantitative changes, with a post-natal relative decrease in the collagen IV and laminin content when compared with the level of BM-associated HSPG. Our results provide circumstantial evidence that the composition of the extracellular matrix (and in particular of the BM) shows age-dependent quantitative changes which may be associated with functional adaptation processes of the developing kidney. The observed matrix composition in the two different congenital nephrotic syndromes suggests various pathomechanisms which may be located either in the molecular structure of the negatively charged molecules (e.g. abnormal sulphatation of HSPG in FCNS) or in the dysregulated synthesis of various matrix components (DMS).