DISTRIBUTION AND ONTOGENY OF TENASCIN IN NORMAL AND CYSTIC HUMAN FETAL KIDNEYS

BACKGROUND: Tenascin is a mesenchymal extracellular matrix glycoprotei n transiently expressed during development, mainly at the site of epit helial-mesenchymal interactions. It is thought to play a key role in m orphogenesis. Little is known about the distribution of tenascin in no rmal human fetal kidney, and, so far, no data have been reported conce rning the distribution of the protein in fetal cystic kidneys. EXPERIM ENTAL DESIGN: Using specific mAb and the immunofluorescence technique, we analyzed the distribution of tenascin in normal human embryonic (n = 3), fetal (n = 15), and mature kidneys (n = 4) and in fetuses affec ted with autosomal recessive polycystic disease (n = 3), autosomal dom inant polycystic disease (n = 3), and cystic dysplasia (n = 3). We com pared the distribution of this protein with that of fibronectin and ty pes I, III, V, and VI, collagens. RESULTS: In normal developing kidney s, tenascin is present in the uninduced blastema and in the mesenchyme around differentiating nephrons. It is homogeneously distributed in t he inner cortex and in the medulla. During maturation, tenascin expres sion persists in the medulla but progressively decreases in the cortex . Tenascin is present in the mesangial area from the S-shaped body sta ge. Both types of polycystic diseases are characterized by a marked an d diffuse increase in cortical and medullary expression of tenascin as well as types III, V, and VI collagen. In cystic dysplasia, two types of changes were observed: (a) increased tenascin and interstitial col lagen expression in the subcapsular strips of condensed mesenchyme; an d (b) heterogeneous medullary tenascin distribution with positive labe ling of the condensed mesenchyme surrounding cysts and primitive ducts and negative labeling of the loose interstitial mesenchyme, contrasti ng with the diffuse accumulation of types III, V, and VI collagen. CON CLUSIONS: In the human fetal kidney, tenascin is expressed by blastema cells and disappears when converted to epithelium. In polycystic dise ases, an early increase in tenascin and interstitial collagen expressi on suggests that renal mesenchyme per se may contribute to the progres sive alteration of the kidney. In cystic dysplasia, phenotypic changes in metanephric blastema indicate inappropriate commitment of blastema cells into interstitial cells, leading to the definitive arrest of ne phrogenesis; the heterogeneity in tenascin medullary expression underl ines the heterogeneity in the mesenchymal cell population.