LOCALIZATION OF EXTRACELLULAR-MATRIX COMPONENTS IN CONGENITAL NEPHROTIC SYNDROMES

While renal tissue from one fetus and a newborn with congenital nephro tic syndrome, Finnish type (FCNS), showed a normal basement membrane ( BM) localization and composition, in another type of congenital nephro tic syndrome, diffuse mesangial sclerosis (DMS), most glomeruli demons trated a completely disorganized matrix. In the latter, hyalinized glo merular segments were composed of irregular deposits of interstitial c ollagens I, III, V, and extensive deposits of heparan sulphate proteog lycan (HSPG), while collagen IV and laminin were completely absent in those areas. Apart from these sclerosed glomerular areas, normal capil larly loops revealed a matrix composition that was comparable to norma l glomeruli. The additional immunolocalization of various extracellula r matrix components during the development of normal human glomeruli r evealed some significant age-dependent changes both in the localizatio n 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 qualita tive changes, but quantitative changes, with a post-natal relative dec rease in the collagen IV and laminin content when compared with the le vel of BM-associated HSPG. Our results provide circumstantial evidence that the composition of the extracellular matrix (and in particular o f the BM) shows age-dependent quantitative changes which may be associ ated with functional adaptation processes of the developing kidney. Th e observed matrix composition in the two different congenital nephroti c syndromes suggests various pathomechanisms which may be located eith er in the molecular structure of the negatively charged molecules (e.g . abnormal sulphatation of HSPG in FCNS) or in the dysregulated synthe sis of various matrix components (DMS).