Distribution and ontogenesis of tenascin in normal and cystic human fetal kidneys.

BACKGROUND

Tenascin is a mesenchymal extracellular matrix glycoprotein transiently expressed during development, mainly at the site of epithelial-mesenchymal interactions. It is thought to play a key role in morphogenesis. Little is known about the distribution of tenascin in normal human fetal kidney, and, so far, no data have been reported concerning the distribution of the protein in fetal cystic kidneys.

EXPERIMENTAL 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 affected with autosomal recessive polycystic disease (n = 3), autosomal dominant polycystic disease (n = 3), and cystic dysplasia (n = 3). We compared the distribution of this protein with that of fibronectin and types I, III, V, and VI collagens.

RESULTS

In normal developing kidneys, tenascin is present in the uninduced blastema and in the mesenchyme around differentiating nephrons. It is homogeneously distributed in the inner cortex and in the medulla. During maturation, tenascin expression persists in the medulla but progressively decreases in the cortex. Tenascin is present in the mesangial area from the S-shaped body stage. Both types of polycystic diseases are characterized by a marked and 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 collagen expression in the subcapsular strips of condensed mesenchyme; and (b) heterogeneous medullary tenascin distribution with positive labeling of the condensed mesenchyme surrounding cysts and primitive ducts and negative labeling of the loose interstitial mesenchyme, contrasting with the diffuse accumulation of types III, V, and VI collagen.

CONCLUSIONS

In the human fetal kidney, tenascin is expressed by blastema cells and disappears when converted to epithelium. In polycystic diseases, an early increase in tenascin and interstitial collagen expression suggests that renal mesenchyme per se may contribute to the progressive 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 nephrogenesis; the heterogeneity in tenascin medullary expression underlines the heterogeneity in the mesenchymal cell population.